Skip to main content
Erschienen in: Journal of Mammary Gland Biology and Neoplasia 4/2008

01.12.2008

IGF Binding Proteins (IGFBPs) and Regulation of Breast Cancer Biology

verfasst von: Claire M. Perks, Jeff M. P. Holly

Erschienen in: Journal of Mammary Gland Biology and Neoplasia | Ausgabe 4/2008

Einloggen, um Zugang zu erhalten

Abstract

The IGFBP family comprises six proteins with high affinity for the IGFs. Changes in the balance of the components of the IGF system may contribute to the progression of breast cancer. In tumours the abundance of IGFBPs relates to the estrogen receptor status and their production in the breast is controlled by hormones, principally estrogen and progesterone. Important interactions occur between IGFBPs and key growth regulators such as TGF-beta, PTEN and EGF which are reviewed. The conflicting observations between the effects of IGFBPs on the risk of breast cancer, in particular IGFBP-3, obtained from epidemiology studies in comparison to in vivo observations are highlighted and potential explanations provided. The functional activity of IGFBPs can also be affected by proteolysis, phosphorylation and glycosylation and the implications of these are described. The IGFs are generally present at levels far in excess of that required for maximal receptor stimulation, and the IGFBPs are critical regulators of their cellular actions. IGFBPs can affect cell function in an IGF-dependent or independent manner. The key mechanisms underlying the intrinsic actions of the IGFBPs are still in debate. IGF bioactivity locally in the breast is influenced not only by local tissue expression and regulation of IGFs, IGFBPs and IGFBP proteases, but also by these factors delivered from the circulation. Finally, the therapeutic potential of IGFBPs-2 and -3 are considered together with key questions that still need to be addressed.
Literatur
1.
Zurück zum Zitat Baxter RC. IGF binding protein-3 and the acid-labile subunit: formation of the ternary complex in vitro and in vivo. Adv Exp Med Biol. 1993;343:237–44.PubMed Baxter RC. IGF binding protein-3 and the acid-labile subunit: formation of the ternary complex in vitro and in vivo. Adv Exp Med Biol. 1993;343:237–44.PubMed
2.
Zurück zum Zitat Twigg SM, Baxter RC. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273(11):6074–9. doi:10.1074/jbc.273.11.6074.PubMed Twigg SM, Baxter RC. Insulin-like growth factor (IGF)-binding protein 5 forms an alternative ternary complex with IGFs and the acid-labile subunit. J Biol Chem. 1998;273(11):6074–9. doi:10.​1074/​jbc.​273.​11.​6074.PubMed
3.
Zurück zum Zitat Figueroa JA, Jackson JG, McGuire WL, Krywicki RF, Yee D. Expression of insulin-like growth factor binding proteins in human breast cancer correlates with estrogen receptor status. J Cell Biochem. 1993;52(2):196–205. doi:10.1002/jcb.240520211.PubMed Figueroa JA, Jackson JG, McGuire WL, Krywicki RF, Yee D. Expression of insulin-like growth factor binding proteins in human breast cancer correlates with estrogen receptor status. J Cell Biochem. 1993;52(2):196–205. doi:10.​1002/​jcb.​240520211.PubMed
4.
Zurück zum Zitat Chen JC, Shao ZM, Sheikh MS, Hussain A, LeRoith D, Roberts CT Jr, et al. Insulin-like growth factor-binding protein enhancement of insulin-like growth factor-I (IGF-I)-mediated DNA synthesis and IGF-I binding in a human breast carcinoma cell line. J Cell Physiol. 1994;158(1):69–78. doi:10.1002/jcp.1041580110.PubMed Chen JC, Shao ZM, Sheikh MS, Hussain A, LeRoith D, Roberts CT Jr, et al. Insulin-like growth factor-binding protein enhancement of insulin-like growth factor-I (IGF-I)-mediated DNA synthesis and IGF-I binding in a human breast carcinoma cell line. J Cell Physiol. 1994;158(1):69–78. doi:10.​1002/​jcp.​1041580110.PubMed
5.
Zurück zum Zitat Ritvos O, Ranta T, Jalkanen J, Suikkari AM, Voutilainen R, Bohn H, et al. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology. 1988;122(5):2150–7.PubMed Ritvos O, Ranta T, Jalkanen J, Suikkari AM, Voutilainen R, Bohn H, et al. Insulin-like growth factor (IGF) binding protein from human decidua inhibits the binding and biological action of IGF-I in cultured choriocarcinoma cells. Endocrinology. 1988;122(5):2150–7.PubMed
6.
Zurück zum Zitat Yee D, Favoni RE, Lippman ME, Powell DR. Identification of insulin-like growth factor binding proteins in breast cancer cells. Breast Cancer Res Treat. 1991;18(1):3–10. doi:10.1007/BF01975437.PubMed Yee D, Favoni RE, Lippman ME, Powell DR. Identification of insulin-like growth factor binding proteins in breast cancer cells. Breast Cancer Res Treat. 1991;18(1):3–10. doi:10.​1007/​BF01975437.PubMed
7.
Zurück zum Zitat Clemmons DR, Camacho-Hubner C, Coronado E, Osborne CK. Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. Endocrinology. 1990;127(6):2679–86.PubMed Clemmons DR, Camacho-Hubner C, Coronado E, Osborne CK. Insulin-like growth factor binding protein secretion by breast carcinoma cell lines: correlation with estrogen receptor status. Endocrinology. 1990;127(6):2679–86.PubMed
8.
Zurück zum Zitat Sheikh MS, Shao ZM, Clemmons DR, LeRoith D, Roberts CT Jr, Fontana JA. Identification of the insulin-like growth factor binding proteins 5 and 6 (IGFBP-5 and 6) in human breast cancer cells. Biochem Biophys Res Commun. 1992;183(3):1003–10. doi:10.1016/S0006-291X(05)80290-6.PubMed Sheikh MS, Shao ZM, Clemmons DR, LeRoith D, Roberts CT Jr, Fontana JA. Identification of the insulin-like growth factor binding proteins 5 and 6 (IGFBP-5 and 6) in human breast cancer cells. Biochem Biophys Res Commun. 1992;183(3):1003–10. doi:10.​1016/​S0006-291X(05)80290-6.PubMed
9.
Zurück zum Zitat Pekonen F, Nyman T, Ilvesmaki V, Partanen S. Insulin-like growth factor binding proteins in human breast cancer tissue. Cancer Res. 1992;52(19):5204–7.PubMed Pekonen F, Nyman T, Ilvesmaki V, Partanen S. Insulin-like growth factor binding proteins in human breast cancer tissue. Cancer Res. 1992;52(19):5204–7.PubMed
10.
Zurück zum Zitat Rocha RL, Hilsenbeck SG, Jackson JG, VanDenBerg CL, Weng C, Lee AV, et al. Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin Cancer Res. 1997;3(1):103–9.PubMed Rocha RL, Hilsenbeck SG, Jackson JG, VanDenBerg CL, Weng C, Lee AV, et al. Insulin-like growth factor binding protein-3 and insulin receptor substrate-1 in breast cancer: correlation with clinical parameters and disease-free survival. Clin Cancer Res. 1997;3(1):103–9.PubMed
11.
Zurück zum Zitat Rocha RL, Hilsenbeck SG, Jackson JG, Lee AV, Figueroa JA, Yee D. Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: detection of higher levels in tumors with poor prognostic features. J Natl Cancer Inst. 1996;88(9):601–6. doi:10.1093/jnci/88.9.601.PubMed Rocha RL, Hilsenbeck SG, Jackson JG, Lee AV, Figueroa JA, Yee D. Correlation of insulin-like growth factor-binding protein-3 messenger RNA with protein expression in primary breast cancer tissues: detection of higher levels in tumors with poor prognostic features. J Natl Cancer Inst. 1996;88(9):601–6. doi:10.​1093/​jnci/​88.​9.​601.PubMed
12.
Zurück zum Zitat Yu H, Levesque MA, Khosravi MJ, Papanastasiou-Diamandi A, Clark GM, Diamandis EP. Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer. Br J Cancer. 1996;74(8):1242–7.PubMed Yu H, Levesque MA, Khosravi MJ, Papanastasiou-Diamandi A, Clark GM, Diamandis EP. Associations between insulin-like growth factors and their binding proteins and other prognostic indicators in breast cancer. Br J Cancer. 1996;74(8):1242–7.PubMed
13.
Zurück zum Zitat Vestey S, Perks C, Sen C, Calder C, Holly J, Winters Z. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and DCIS—implications for clinicopathology and patient outcome. Breast Cancer Res. 2004;7:R119–29. doi:10.1186/bcr963.PubMed Vestey S, Perks C, Sen C, Calder C, Holly J, Winters Z. Immunohistochemical expression of insulin-like growth factor binding protein-3 in invasive breast cancers and DCIS—implications for clinicopathology and patient outcome. Breast Cancer Res. 2004;7:R119–29. doi:10.​1186/​bcr963.PubMed
16.
Zurück zum Zitat Busund LT, Richardsen E, Busund R, Ukkonen T, Bjornsen T, Busch C, et al. Significant expression of IGFBP2 in breast cancer compared with benign lesions. J Clin Pathol. 2005;58(4):361–6. doi:10.1136/jcp.2004.020834.PubMed Busund LT, Richardsen E, Busund R, Ukkonen T, Bjornsen T, Busch C, et al. Significant expression of IGFBP2 in breast cancer compared with benign lesions. J Clin Pathol. 2005;58(4):361–6. doi:10.​1136/​jcp.​2004.​020834.PubMed
17.
Zurück zum Zitat Yee D, Sharma J, Hilsenbeck SG. Prognostic significance of insulin-like growth factor-binding protein expression in axillary lymph node-negative breast cancer. J Natl Cancer Inst. 1994;86(23):1785–9. doi:10.1093/jnci/86.23.1785.PubMed Yee D, Sharma J, Hilsenbeck SG. Prognostic significance of insulin-like growth factor-binding protein expression in axillary lymph node-negative breast cancer. J Natl Cancer Inst. 1994;86(23):1785–9. doi:10.​1093/​jnci/​86.​23.​1785.PubMed
18.
Zurück zum Zitat Mita K, Zhang Z, Ando Y, Toyama T, Hamaguchi M, Kobayashi S, et al. Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer. Jpn J Clin Oncol. 2007;37(8):575–82. doi:10.1093/jjco/hym066.PubMed Mita K, Zhang Z, Ando Y, Toyama T, Hamaguchi M, Kobayashi S, et al. Prognostic significance of insulin-like growth factor binding protein (IGFBP)-4 and IGFBP-5 expression in breast cancer. Jpn J Clin Oncol. 2007;37(8):575–82. doi:10.​1093/​jjco/​hym066.PubMed
20.
Zurück zum Zitat Bruning PF, Van Doorn J, Bonfrer JM, Van Noord PA, Korse CM, Linders TC, et al. Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer. 1995;62(3):266–70. doi:10.1002/ijc.2910620306.PubMed Bruning PF, Van Doorn J, Bonfrer JM, Van Noord PA, Korse CM, Linders TC, et al. Insulin-like growth-factor-binding protein 3 is decreased in early-stage operable pre-menopausal breast cancer. Int J Cancer. 1995;62(3):266–70. doi:10.​1002/​ijc.​2910620306.PubMed
21.
Zurück zum Zitat Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998;351(9113):1393–6. doi:10.1016/S0140-6736(97)10384-1.PubMed Hankinson SE, Willett WC, Colditz GA, Hunter DJ, Michaud DS, Deroo B, et al. Circulating concentrations of insulin-like growth factor-I and risk of breast cancer. Lancet. 1998;351(9113):1393–6. doi:10.​1016/​S0140-6736(97)10384-1.PubMed
22.
Zurück zum Zitat Schernhammer ES, Holly JM, Pollak MN, Hankinson SE. Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14(3):699–704. doi:10.1158/1055-9965.EPI-04-0561.PubMed Schernhammer ES, Holly JM, Pollak MN, Hankinson SE. Circulating levels of insulin-like growth factors, their binding proteins, and breast cancer risk. Cancer Epidemiol Biomarkers Prev. 2005;14(3):699–704. doi:10.​1158/​1055-9965.​EPI-04-0561.PubMed
23.
Zurück zum Zitat Keinan-Boker L, Bueno De Mesquita HB, Kaaks R, Van Gils CH, Van Noord PA, Rinaldi S, et al. Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C-peptide and risk of postmenopausal breast cancer. Int J Cancer. 2003;106(1):90–5. doi:10.1002/ijc.11193.PubMed Keinan-Boker L, Bueno De Mesquita HB, Kaaks R, Van Gils CH, Van Noord PA, Rinaldi S, et al. Circulating levels of insulin-like growth factor I, its binding proteins -1,-2, -3, C-peptide and risk of postmenopausal breast cancer. Int J Cancer. 2003;106(1):90–5. doi:10.​1002/​ijc.​11193.PubMed
24.
Zurück zum Zitat Gronbaek H, Flyvbjerg A, Mellemkjaer L, Tjonneland A, Christensen J, Sorensen HT, et al. Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2004;13(11 Pt 1):1759–64.PubMed Gronbaek H, Flyvbjerg A, Mellemkjaer L, Tjonneland A, Christensen J, Sorensen HT, et al. Serum insulin-like growth factors, insulin-like growth factor binding proteins, and breast cancer risk in postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2004;13(11 Pt 1):1759–64.PubMed
25.
26.
Zurück zum Zitat Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–53. doi:10.1016/S0140-6736(04)16044-3.PubMed Renehan AG, Zwahlen M, Minder C, O’Dwyer ST, Shalet SM, Egger M. Insulin-like growth factor (IGF)-I, IGF binding protein-3, and cancer risk: systematic review and meta-regression analysis. Lancet. 2004;363(9418):1346–53. doi:10.​1016/​S0140-6736(04)16044-3.PubMed
27.
Zurück zum Zitat McCaig C, Perks CM, Holly JM. Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. J Cell Sci. 2002;115(Pt 22):4293–303. doi:10.1242/jcs.00097.PubMed McCaig C, Perks CM, Holly JM. Intrinsic actions of IGFBP-3 and IGFBP-5 on Hs578T breast cancer epithelial cells: inhibition or accentuation of attachment and survival is dependent upon the presence of fibronectin. J Cell Sci. 2002;115(Pt 22):4293–303. doi:10.​1242/​jcs.​00097.PubMed
28.
Zurück zum Zitat Al-Zahrani A, Sandhu MS, Luben RN, Thompson D, Baynes C, Pooley KA, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15(1):1–10. doi:10.1093/hmg/ddi398.PubMed Al-Zahrani A, Sandhu MS, Luben RN, Thompson D, Baynes C, Pooley KA, et al. IGF1 and IGFBP3 tagging polymorphisms are associated with circulating levels of IGF1, IGFBP3 and risk of breast cancer. Hum Mol Genet. 2006;15(1):1–10. doi:10.​1093/​hmg/​ddi398.PubMed
29.
Zurück zum Zitat Ren Z, Cai Q, Shu XO, Cai H, Li C, Yu H, et al. Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. Cancer Epidemiol Biomarkers Prev. 2004;13(8):1290–5.PubMed Ren Z, Cai Q, Shu XO, Cai H, Li C, Yu H, et al. Genetic polymorphisms in the IGFBP3 gene: association with breast cancer risk and blood IGFBP-3 protein levels among Chinese women. Cancer Epidemiol Biomarkers Prev. 2004;13(8):1290–5.PubMed
30.
Zurück zum Zitat Slattery ML, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007;104(2):197–209. doi:10.1007/s10549-006-9403-9.PubMed Slattery ML, Sweeney C, Wolff R, Herrick J, Baumgartner K, Giuliano A, et al. Genetic variation in IGF1, IGFBP3, IRS1, IRS2 and risk of breast cancer in women living in Southwestern United States. Breast Cancer Res Treat. 2007;104(2):197–209. doi:10.​1007/​s10549-006-9403-9.PubMed
31.
Zurück zum Zitat Wagner K, Hemminki K, Israelsson E, Grzybowska E, Soderberg M, Pamula J, et al. Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer. Breast Cancer Res Treat. 2005;92(2):133–40. doi:10.1007/s10549-005-2417-x.PubMed Wagner K, Hemminki K, Israelsson E, Grzybowska E, Soderberg M, Pamula J, et al. Polymorphisms in the IGF-1 and IGFBP 3 promoter and the risk of breast cancer. Breast Cancer Res Treat. 2005;92(2):133–40. doi:10.​1007/​s10549-005-2417-x.PubMed
32.
Zurück zum Zitat Canzian F, McKay JD, Cleveland RJ, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer. 2006;94(2):299–307. doi:10.1038/sj.bjc.6602936.PubMed Canzian F, McKay JD, Cleveland RJ, Dossus L, Biessy C, Rinaldi S, et al. Polymorphisms of genes coding for insulin-like growth factor 1 and its major binding proteins, circulating levels of IGF-I and IGFBP-3 and breast cancer risk: results from the EPIC study. Br J Cancer. 2006;94(2):299–307. doi:10.​1038/​sj.​bjc.​6602936.PubMed
33.
Zurück zum Zitat Cheng I, Penney KL, Stram DO, Le Marchand L, Giorgi E, Haiman CA, et al. Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1993–7. doi:10.1158/1055-9965.EPI-06-0361.PubMed Cheng I, Penney KL, Stram DO, Le Marchand L, Giorgi E, Haiman CA, et al. Haplotype-based association studies of IGFBP1 and IGFBP3 with prostate and breast cancer risk: the multiethnic cohort. Cancer Epidemiol Biomarkers Prev. 2006;15(10):1993–7. doi:10.​1158/​1055-9965.​EPI-06-0361.PubMed
34.
Zurück zum Zitat Schernhammer ES, Hankinson SE, Hunter DJ, Blouin MJ, Pollak MN. Polymorphic variation at the -202 locus in IGFBP3: influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk. Int J Cancer. 2003;107(1):60–4. doi:10.1002/ijc.11358.PubMed Schernhammer ES, Hankinson SE, Hunter DJ, Blouin MJ, Pollak MN. Polymorphic variation at the -202 locus in IGFBP3: influence on serum levels of insulin-like growth factors, interaction with plasma retinol and vitamin D and breast cancer risk. Int J Cancer. 2003;107(1):60–4. doi:10.​1002/​ijc.​11358.PubMed
35.
Zurück zum Zitat Sigurdson AJ, Hauptmann M, Chatterjee N, Alexander BH, Doody MM, Rutter JL, et al. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes. BMC Cancer. 2004;4:9. doi:10.1186/1471-2407-4-9.PubMed Sigurdson AJ, Hauptmann M, Chatterjee N, Alexander BH, Doody MM, Rutter JL, et al. Kin-cohort estimates for familial breast cancer risk in relation to variants in DNA base excision repair, BRCA1 interacting and growth factor genes. BMC Cancer. 2004;4:9. doi:10.​1186/​1471-2407-4-9.PubMed
36.
Zurück zum Zitat Garner CP, Ding YC, John EM, Ingles SA, Olopade OI, Huo D, et al. Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent. Hum Genet. 2008;123(3):247–55. doi:10.1007/s00439-008-0468-x.PubMed Garner CP, Ding YC, John EM, Ingles SA, Olopade OI, Huo D, et al. Genetic variation in IGFBP2 and IGFBP5 is associated with breast cancer in populations of African descent. Hum Genet. 2008;123(3):247–55. doi:10.​1007/​s00439-008-0468-x.PubMed
37.
38.
Zurück zum Zitat Lai JH, Vesprini D, Zhang W, Yaffe MJ, Pollak M, Narod SA. A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammographic breast density. Cancer Epidemiol Biomarkers Prev. 2004;13(4):573–82.PubMed Lai JH, Vesprini D, Zhang W, Yaffe MJ, Pollak M, Narod SA. A polymorphic locus in the promoter region of the IGFBP3 gene is related to mammographic breast density. Cancer Epidemiol Biomarkers Prev. 2004;13(4):573–82.PubMed
39.
Zurück zum Zitat dos Santos Silva I, Johnson N, De Stavola B, Torres-Mejia G, Fletcher O, Allen DS, et al. The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2006;15(3):449–55. doi:10.1158/1055-9965.EPI-05-0555.PubMed dos Santos Silva I, Johnson N, De Stavola B, Torres-Mejia G, Fletcher O, Allen DS, et al. The insulin-like growth factor system and mammographic features in premenopausal and postmenopausal women. Cancer Epidemiol Biomarkers Prev. 2006;15(3):449–55. doi:10.​1158/​1055-9965.​EPI-05-0555.PubMed
40.
Zurück zum Zitat Tamimi RM, Cox DG, Kraft P, Pollak MN, Haiman CA, Cheng I, et al. Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study. Breast Cancer Res. 2007;9(1):R18. doi:10.1186/bcr1655.PubMed Tamimi RM, Cox DG, Kraft P, Pollak MN, Haiman CA, Cheng I, et al. Common genetic variation in IGF1, IGFBP-1, and IGFBP-3 in relation to mammographic density: a cross-sectional study. Breast Cancer Res. 2007;9(1):R18. doi:10.​1186/​bcr1655.PubMed
41.
Zurück zum Zitat Diorio C, Brisson J, Berube S, Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev. 2008;17(4):880–8. doi:10.1158/1055-9965.EPI-07-2500.PubMed Diorio C, Brisson J, Berube S, Pollak M. Genetic polymorphisms involved in insulin-like growth factor (IGF) pathway in relation to mammographic breast density and IGF levels. Cancer Epidemiol Biomarkers Prev. 2008;17(4):880–8. doi:10.​1158/​1055-9965.​EPI-07-2500.PubMed
42.
Zurück zum Zitat Stewart AJ, Johnson MD, May FE, Westley BR. Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem. 1990;265(34):21172–8.PubMed Stewart AJ, Johnson MD, May FE, Westley BR. Role of insulin-like growth factors and the type I insulin-like growth factor receptor in the estrogen-stimulated proliferation of human breast cancer cells. J Biol Chem. 1990;265(34):21172–8.PubMed
44.
Zurück zum Zitat Owens PC, Gill PG, De Young NJ, Weger MA, Knowles SE, Moyse KJ. Estrogen and progesterone regulate secretion of insulin-like growth factor binding proteins by human breast cancer cells. Biochem Biophys Res Commun. 1993;193(2):467–73. doi:10.1006/bbrc.1993.1647.PubMed Owens PC, Gill PG, De Young NJ, Weger MA, Knowles SE, Moyse KJ. Estrogen and progesterone regulate secretion of insulin-like growth factor binding proteins by human breast cancer cells. Biochem Biophys Res Commun. 1993;193(2):467–73. doi:10.​1006/​bbrc.​1993.​1647.PubMed
45.
Zurück zum Zitat Pratt SE, Pollak MN. Estrogen and antiestrogen modulation of MCF7 human breast cancer cell proliferation is associated with specific alterations in accumulation of insulin-like growth factor-binding proteins in conditioned media. Cancer Res. 1993;53(21):5193–8.PubMed Pratt SE, Pollak MN. Estrogen and antiestrogen modulation of MCF7 human breast cancer cell proliferation is associated with specific alterations in accumulation of insulin-like growth factor-binding proteins in conditioned media. Cancer Res. 1993;53(21):5193–8.PubMed
46.
Zurück zum Zitat Vignon F, Bardon S, Chalbos D, Rochefort H. Antiestrogenic effect of R5020, a synthetic progestin in human breast cancer cells in culture. J Clin Endocrinol Metab. 1993;56:1124–30. Vignon F, Bardon S, Chalbos D, Rochefort H. Antiestrogenic effect of R5020, a synthetic progestin in human breast cancer cells in culture. J Clin Endocrinol Metab. 1993;56:1124–30.
47.
Zurück zum Zitat Parisot JP, Leeding KS, Hu XF, DeLuise M, Zalcberg JR, Bach LA. Induction of insulin-like growth factor binding protein expression by ICI 182,780 in a tamoxifen-resistant human breast cancer cell line. Breast Cancer Res Treat. 1999;55(3):231–42. doi:10.1023/A:1006274712664.PubMed Parisot JP, Leeding KS, Hu XF, DeLuise M, Zalcberg JR, Bach LA. Induction of insulin-like growth factor binding protein expression by ICI 182,780 in a tamoxifen-resistant human breast cancer cell line. Breast Cancer Res Treat. 1999;55(3):231–42. doi:10.​1023/​A:​1006274712664.PubMed
48.
Zurück zum Zitat Milewicz T, Gregoraszczuk EL, Sztefko K, Augustowska K, Krzysiek J, Rys J. Lack of synergy between estrogen and progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion by both hormone-dependent and hormone-independent breast cancer explants in vitro. Effect of tamoxifen and mifepristone (RU 486). Growth Horm IGF Res. 2005;15(2):140–7. doi:10.1016/j.ghir.2004.12.006.PubMed Milewicz T, Gregoraszczuk EL, Sztefko K, Augustowska K, Krzysiek J, Rys J. Lack of synergy between estrogen and progesterone on local IGF-I, IGFBP-3 and IGFBP-2 secretion by both hormone-dependent and hormone-independent breast cancer explants in vitro. Effect of tamoxifen and mifepristone (RU 486). Growth Horm IGF Res. 2005;15(2):140–7. doi:10.​1016/​j.​ghir.​2004.​12.​006.PubMed
49.
Zurück zum Zitat Juncker-Jensen A, Lykkesfeldt AE, Worm J, Ralfkiaer U, Espelund U, Jepsen JS. Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator. Growth Horm IGF Res. 2006;16(4):224–39. doi:10.1016/j.ghir.2006.06.005.PubMed Juncker-Jensen A, Lykkesfeldt AE, Worm J, Ralfkiaer U, Espelund U, Jepsen JS. Insulin-like growth factor binding protein 2 is a marker for antiestrogen resistant human breast cancer cell lines but is not a major growth regulator. Growth Horm IGF Res. 2006;16(4):224–39. doi:10.​1016/​j.​ghir.​2006.​06.​005.PubMed
51.
Zurück zum Zitat Lonning PE, Hall K, Aakvaag A, Lien EA. Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients. Cancer Res. 1992;52(17):4719–23.PubMed Lonning PE, Hall K, Aakvaag A, Lien EA. Influence of tamoxifen on plasma levels of insulin-like growth factor I and insulin-like growth factor binding protein I in breast cancer patients. Cancer Res. 1992;52(17):4719–23.PubMed
52.
Zurück zum Zitat Pollak MN, Huynh HT, Lefebvre SP. Tamoxifen reduces serum insulin-like growth factor I (IGF-I). Breast Cancer Res Treat. 1992;22(1):91–100. doi:10.1007/BF01833337.PubMed Pollak MN, Huynh HT, Lefebvre SP. Tamoxifen reduces serum insulin-like growth factor I (IGF-I). Breast Cancer Res Treat. 1992;22(1):91–100. doi:10.​1007/​BF01833337.PubMed
53.
Zurück zum Zitat Gronbaek H, Tanos V, Meirow D, Peretz T, Raz I, Flyvbjerg A. Effects of tamoxifen on insulin-like growth factors, IGF binding proteins and IGFBP-3 proteolysis in breast cancer patients. Anticancer Res. 2003;23(3C):2815–20.PubMed Gronbaek H, Tanos V, Meirow D, Peretz T, Raz I, Flyvbjerg A. Effects of tamoxifen on insulin-like growth factors, IGF binding proteins and IGFBP-3 proteolysis in breast cancer patients. Anticancer Res. 2003;23(3C):2815–20.PubMed
55.
Zurück zum Zitat Helle SI, Mietlowski W, Guastalla JP, Szakolczai I, Bajetta E, Sommer H, et al. Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy. Eur J Cancer. 2005;41(5):694–701. doi:10.1016/j.ejca.2004.12.015.PubMed Helle SI, Mietlowski W, Guastalla JP, Szakolczai I, Bajetta E, Sommer H, et al. Effects of tamoxifen and octreotide LAR on the IGF-system compared with tamoxifen monotherapy. Eur J Cancer. 2005;41(5):694–701. doi:10.​1016/​j.​ejca.​2004.​12.​015.PubMed
56.
Zurück zum Zitat Lawrence JB, Conover CA, Haddad TC, Ingle JN, Reid JM, Ames MM, et al. Evaluation of continuous infusion suramin in metastatic breast cancer: impact on plasma levels of insulin-like growth factors (IGFs) and IGF-binding proteins. Clin Cancer Res. 1997;3(10):1713–20.PubMed Lawrence JB, Conover CA, Haddad TC, Ingle JN, Reid JM, Ames MM, et al. Evaluation of continuous infusion suramin in metastatic breast cancer: impact on plasma levels of insulin-like growth factors (IGFs) and IGF-binding proteins. Clin Cancer Res. 1997;3(10):1713–20.PubMed
57.
Zurück zum Zitat Lien EA, Johannessen DC, Aakvaag A, Lonning PE. Influence of tamoxifen, aminoglutethimide and goserelin on human plasma IGF-I levels in breast cancer patients. J Steroid Biochem Mol Biol 1992;41(3–8):541–3.PubMed Lien EA, Johannessen DC, Aakvaag A, Lonning PE. Influence of tamoxifen, aminoglutethimide and goserelin on human plasma IGF-I levels in breast cancer patients. J Steroid Biochem Mol Biol 1992;41(3–8):541–3.PubMed
58.
Zurück zum Zitat Bajetta E, Ferrari L, Celio L, Mariani L, Miceli R, Di Leo A, et al. The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. J Steroid Biochem Mol Biol. 1997;63(4–6):261–7. doi:10.1016/S0960-0760(97)00120-9.PubMed Bajetta E, Ferrari L, Celio L, Mariani L, Miceli R, Di Leo A, et al. The aromatase inhibitor letrozole in advanced breast cancer: effects on serum insulin-like growth factor (IGF)-I and IGF-binding protein-3 levels. J Steroid Biochem Mol Biol. 1997;63(4–6):261–7. doi:10.​1016/​S0960-0760(97)00120-9.PubMed
59.
Zurück zum Zitat Reed MJ, Christodoulides A, Koistinen R, Seppala M, Teale JD, Ghilchik MW. The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer. Int J Cancer. 1992;52(2):208–12. doi:10.1002/ijc.2910520209.PubMed Reed MJ, Christodoulides A, Koistinen R, Seppala M, Teale JD, Ghilchik MW. The effect of endocrine therapy with medroxyprogesterone acetate, 4-hydroxyandrostenedione or tamoxifen on plasma concentrations of insulin-like growth factor (IGF)-I, IGF-II and IGFBP-1 in women with advanced breast cancer. Int J Cancer. 1992;52(2):208–12. doi:10.​1002/​ijc.​2910520209.PubMed
60.
Zurück zum Zitat Helle SI, Jonat W, Giurescu M, Ekse D, Holly JM, Lonning PE. Influence of treatment with onapristone on the IGF-system in breast cancer patients. J Steroid Biochem Mol Biol. 1998;66(3):159–63. doi:10.1016/S0960-0760(98)00046-6.PubMed Helle SI, Jonat W, Giurescu M, Ekse D, Holly JM, Lonning PE. Influence of treatment with onapristone on the IGF-system in breast cancer patients. J Steroid Biochem Mol Biol. 1998;66(3):159–63. doi:10.​1016/​S0960-0760(98)00046-6.PubMed
61.
Zurück zum Zitat Frost VJ, Helle SI, Lonning PE, van der Stappen JW, Holly JM. Effects of treatment with megestrol acetate, aminoglutethimide, or formestane on insulin-like growth factor (IGF) I and II, IGF-binding proteins (IGFBPs), and IGFBP-3 protease status in patients with advanced breast cancer. J Clin Endocrinol Metab. 1996;81(6):2216–21. doi:10.1210/jc.81.6.2216.PubMed Frost VJ, Helle SI, Lonning PE, van der Stappen JW, Holly JM. Effects of treatment with megestrol acetate, aminoglutethimide, or formestane on insulin-like growth factor (IGF) I and II, IGF-binding proteins (IGFBPs), and IGFBP-3 protease status in patients with advanced breast cancer. J Clin Endocrinol Metab. 1996;81(6):2216–21. doi:10.​1210/​jc.​81.​6.​2216.PubMed
62.
Zurück zum Zitat Perks CM, Holly JM. IGFBPs and breast cancer. Breast Dis. 2003;17:91–104.PubMed Perks CM, Holly JM. IGFBPs and breast cancer. Breast Dis. 2003;17:91–104.PubMed
63.
Zurück zum Zitat James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol. 1996;58(4):395–401. doi:10.1016/0960-0760(96)00048-9.PubMed James SY, Mackay AG, Colston KW. Effects of 1,25 dihydroxyvitamin D3 and its analogues on induction of apoptosis in breast cancer cells. J Steroid Biochem Mol Biol. 1996;58(4):395–401. doi:10.​1016/​0960-0760(96)00048-9.PubMed
64.
Zurück zum Zitat Towsend K, Trevino V, Falciani F, Stewart PM, Hewison M, Campbell MJ. Identification of VDR-responsive gene signatures in breast cancer cells. Oncology. 2006;71(1–2):111–23. doi:10.1159/000100989.PubMed Towsend K, Trevino V, Falciani F, Stewart PM, Hewison M, Campbell MJ. Identification of VDR-responsive gene signatures in breast cancer cells. Oncology. 2006;71(1–2):111–23. doi:10.​1159/​000100989.PubMed
65.
Zurück zum Zitat Danforth DN Jr, Sgagias MK. Tumor necrosis factor alpha enhances secretion of transforming growth factor beta2 in MCF-7 breast cancer cells. Clin Cancer Res. 1996;2(5):827–35.PubMed Danforth DN Jr, Sgagias MK. Tumor necrosis factor alpha enhances secretion of transforming growth factor beta2 in MCF-7 breast cancer cells. Clin Cancer Res. 1996;2(5):827–35.PubMed
66.
Zurück zum Zitat Koli K, Keski-Oja J. 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. Cancer Res. 1995;55(7):1540–6.PubMed Koli K, Keski-Oja J. 1,25-Dihydroxyvitamin D3 enhances the expression of transforming growth factor beta 1 and its latent form binding protein in cultured breast carcinoma cells. Cancer Res. 1995;55(7):1540–6.PubMed
68.
Zurück zum Zitat Lai LC, Erbas H, Meadows KA, Lennard TW, Holly JM. Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships with insulin-like growth factors I and II and transforming growth factor-beta 1 and 2. Cancer Lett. 1996;110(1–2):207–12. doi:10.1016/S0304-3835(96)04497-7.PubMed Lai LC, Erbas H, Meadows KA, Lennard TW, Holly JM. Insulin-like growth factor binding protein-3 in breast cyst fluid: relationships with insulin-like growth factors I and II and transforming growth factor-beta 1 and 2. Cancer Lett. 1996;110(1–2):207–12. doi:10.​1016/​S0304-3835(96)04497-7.PubMed
69.
Zurück zum Zitat McCaig C, Fowler CA, Laurence NJ, Lai T, Savage PB, Holly JM, et al. Differential interactions between IGFBP-3 and transforming growth factor-beta (TGF-beta) in normal vs cancerous breast epithelial cells. Br J Cancer. 2002;86(12):1963–9. doi:10.1038/sj.bjc.6600355.PubMed McCaig C, Fowler CA, Laurence NJ, Lai T, Savage PB, Holly JM, et al. Differential interactions between IGFBP-3 and transforming growth factor-beta (TGF-beta) in normal vs cancerous breast epithelial cells. Br J Cancer. 2002;86(12):1963–9. doi:10.​1038/​sj.​bjc.​6600355.PubMed
70.
Zurück zum Zitat Salahifar H, Baxter RC, Martin JL. Differential regulation of insulin-like growth factor-binding protein-3 protease activity in MCF-7 breast cancer cells by estrogen and transforming growth factor-beta1. Endocrinology. 2000;141(9):3104–10. doi:10.1210/en.141.9.3104.PubMed Salahifar H, Baxter RC, Martin JL. Differential regulation of insulin-like growth factor-binding protein-3 protease activity in MCF-7 breast cancer cells by estrogen and transforming growth factor-beta1. Endocrinology. 2000;141(9):3104–10. doi:10.​1210/​en.​141.​9.​3104.PubMed
71.
Zurück zum Zitat Martin JL, Weenink SM, Baxter RC. Insulin-like growth factor-binding protein-3 potentiates epidermal growth factor action in MCF-10A mammary epithelial cells. Involvement of p44/42 and p38 mitogen-activated protein kinases. J Biol Chem. 2003;278(5):2969–76. doi:10.1074/jbc.M210739200.PubMed Martin JL, Weenink SM, Baxter RC. Insulin-like growth factor-binding protein-3 potentiates epidermal growth factor action in MCF-10A mammary epithelial cells. Involvement of p44/42 and p38 mitogen-activated protein kinases. J Biol Chem. 2003;278(5):2969–76. doi:10.​1074/​jbc.​M210739200.PubMed
72.
Zurück zum Zitat Butt AJ, Martin JL, Dickson KA, McDougall F, Firth SM, Baxter RC. Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling. J Clin Endocrinol Metab. 2004;89(4):1950–6. doi:10.1210/jc.2003-030914.PubMed Butt AJ, Martin JL, Dickson KA, McDougall F, Firth SM, Baxter RC. Insulin-like growth factor binding protein-3 expression is associated with growth stimulation of T47D human breast cancer cells: the role of altered epidermal growth factor signaling. J Clin Endocrinol Metab. 2004;89(4):1950–6. doi:10.​1210/​jc.​2003-030914.PubMed
73.
Zurück zum Zitat Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118(7):2609–19.PubMed Guix M, Faber AC, Wang SE, Olivares MG, Song Y, Qu S, et al. Acquired resistance to EGFR tyrosine kinase inhibitors in cancer cells is mediated by loss of IGF-binding proteins. J Clin Invest. 2008;118(7):2609–19.PubMed
74.
Zurück zum Zitat Moorehead RA, Hojilla CV, De Belle I, Wood GA, Fata JE, Adamson ED, et al. Insulin-like growth factor-II regulates PTEN expression in the mammary gland. J Biol Chem. 2003;278(50):50422–7. doi:10.1074/jbc.M306894200.PubMed Moorehead RA, Hojilla CV, De Belle I, Wood GA, Fata JE, Adamson ED, et al. Insulin-like growth factor-II regulates PTEN expression in the mammary gland. J Biol Chem. 2003;278(50):50422–7. doi:10.​1074/​jbc.​M306894200.PubMed
75.
76.
Zurück zum Zitat Mehrian-Shai R, Chen CD, Shi T, Horvath S, Nelson SF, Reichardt JK, et al. Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer. Proc Natl Acad Sci U S A. 2007;104(13):5563–8. doi:10.1073/pnas.0609139104.PubMed Mehrian-Shai R, Chen CD, Shi T, Horvath S, Nelson SF, Reichardt JK, et al. Insulin growth factor-binding protein 2 is a candidate biomarker for PTEN status and PI3K/Akt pathway activation in glioblastoma and prostate cancer. Proc Natl Acad Sci U S A. 2007;104(13):5563–8. doi:10.​1073/​pnas.​0609139104.PubMed
77.
Zurück zum Zitat Frommer KW, Reichenmiller K, Schutt BS, Hoeflich A, Ranke MB, Dodt G, et al. IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. J Mol Endocrinol. 2006;37(1):13–23. doi:10.1677/jme.1.01955.PubMed Frommer KW, Reichenmiller K, Schutt BS, Hoeflich A, Ranke MB, Dodt G, et al. IGF-independent effects of IGFBP-2 on the human breast cancer cell line Hs578T. J Mol Endocrinol. 2006;37(1):13–23. doi:10.​1677/​jme.​1.​01955.PubMed
78.
Zurück zum Zitat Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A. 1999;96(6):3149–53. doi:10.1073/pnas.96.6.3149.PubMed Lawrence JB, Oxvig C, Overgaard MT, Sottrup-Jensen L, Gleich GJ, Hays LG, et al. The insulin-like growth factor (IGF)-dependent IGF binding protein-4 protease secreted by human fibroblasts is pregnancy-associated plasma protein-A. Proc Natl Acad Sci U S A. 1999;96(6):3149–53. doi:10.​1073/​pnas.​96.​6.​3149.PubMed
79.
Zurück zum Zitat Busby WH Jr, Nam TJ, Moralez A, Smith C, Jennings M, Clemmons DR. The complement component C1s is the protease that accounts for cleavage of insulin-like growth factor-binding protein-5 in fibroblast medium. J Biol Chem. 2000;275(48):37638–44. doi:10.1074/jbc.M006107200.PubMed Busby WH Jr, Nam TJ, Moralez A, Smith C, Jennings M, Clemmons DR. The complement component C1s is the protease that accounts for cleavage of insulin-like growth factor-binding protein-5 in fibroblast medium. J Biol Chem. 2000;275(48):37638–44. doi:10.​1074/​jbc.​M006107200.PubMed
80.
Zurück zum Zitat Mohan S, Thompson GR, Amaar YG, Hathaway G, Tschesche H, Baylink DJ. ADAM-9 is an insulin-like growth factor binding protein-5 protease produced and secreted by human osteoblasts. Biochemistry. 2002;41(51):15394–403. doi:10.1021/bi026458q.PubMed Mohan S, Thompson GR, Amaar YG, Hathaway G, Tschesche H, Baylink DJ. ADAM-9 is an insulin-like growth factor binding protein-5 protease produced and secreted by human osteoblasts. Biochemistry. 2002;41(51):15394–403. doi:10.​1021/​bi026458q.PubMed
81.
Zurück zum Zitat Overgaard MT, Boldt HB, Laursen LS, Sottrup-Jensen L, Conover CA, Oxvig C. Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase. J Biol Chem. 2001;276(24):21849–53. doi:10.1074/jbc.M102191200.PubMed Overgaard MT, Boldt HB, Laursen LS, Sottrup-Jensen L, Conover CA, Oxvig C. Pregnancy-associated plasma protein-A2 (PAPP-A2), a novel insulin-like growth factor-binding protein-5 proteinase. J Biol Chem. 2001;276(24):21849–53. doi:10.​1074/​jbc.​M102191200.PubMed
82.
Zurück zum Zitat Hsieh ML, Charlesworth MC, Goodmanson M, Zhang S, Seay T, Klee GG, et al. Expression of human prostate-specific glandular kallikrein protein (hK2) in the breast cancer cell line T47-D. Cancer Res. 1997;57(13):2651–6.PubMed Hsieh ML, Charlesworth MC, Goodmanson M, Zhang S, Seay T, Klee GG, et al. Expression of human prostate-specific glandular kallikrein protein (hK2) in the breast cancer cell line T47-D. Cancer Res. 1997;57(13):2651–6.PubMed
83.
Zurück zum Zitat Magklara A, Scorilas A, Lopez-Otin C, Vizoso F, Ruibal A, Diamandis EP. Human glandular kallikrein in breast milk, amniotic fluid, and breast cyst fluid. Clin Chem. 1999;45(10):1774–80.PubMed Magklara A, Scorilas A, Lopez-Otin C, Vizoso F, Ruibal A, Diamandis EP. Human glandular kallikrein in breast milk, amniotic fluid, and breast cyst fluid. Clin Chem. 1999;45(10):1774–80.PubMed
84.
Zurück zum Zitat Diamandis EP. Prostate specific antigen—new applications in breast and other cancers. Anticancer Res. 1996;16(6C):3983–4.PubMed Diamandis EP. Prostate specific antigen—new applications in breast and other cancers. Anticancer Res. 1996;16(6C):3983–4.PubMed
85.
Zurück zum Zitat Yu H, Diamandis EP, Levesque M, Giai M, Roagna R, Ponzone R, et al. Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue. Breast Cancer Res Treat. 1996;40(2):171–8. doi:10.1007/BF01806212.PubMed Yu H, Diamandis EP, Levesque M, Giai M, Roagna R, Ponzone R, et al. Prostate specific antigen in breast cancer, benign breast disease and normal breast tissue. Breast Cancer Res Treat. 1996;40(2):171–8. doi:10.​1007/​BF01806212.PubMed
86.
Zurück zum Zitat Paliouras M, Diamandis EP. Coordinated steroid hormone-dependent and independent expression of multiple kallikreins in breast cancer cell lines. Breast Cancer Res Treat. 2007;102(1):7–18. doi:10.1007/s10549-006-9312-y.PubMed Paliouras M, Diamandis EP. Coordinated steroid hormone-dependent and independent expression of multiple kallikreins in breast cancer cell lines. Breast Cancer Res Treat. 2007;102(1):7–18. doi:10.​1007/​s10549-006-9312-y.PubMed
87.
Zurück zum Zitat Paliouras M, Diamandis EP. Intracellular signaling pathways regulate hormone-dependent kallikrein gene expression. Tumour Biol. 2008;29(2):63–75. doi:10.1159/000135686.PubMed Paliouras M, Diamandis EP. Intracellular signaling pathways regulate hormone-dependent kallikrein gene expression. Tumour Biol. 2008;29(2):63–75. doi:10.​1159/​000135686.PubMed
89.
Zurück zum Zitat Rehault S, Monget P, Mazerbourg S, Tremblay R, Gutman N, Gauthier F, et al. Insulin-like growth factor binding proteins (IGFBPs) as potential physiological substrates for human kallikreins hK2 and hK3. Eur J Biochem. 2001;268(10):2960–8. doi:10.1046/j.1432-1327.2001.02185.x.PubMed Rehault S, Monget P, Mazerbourg S, Tremblay R, Gutman N, Gauthier F, et al. Insulin-like growth factor binding proteins (IGFBPs) as potential physiological substrates for human kallikreins hK2 and hK3. Eur J Biochem. 2001;268(10):2960–8. doi:10.​1046/​j.​1432-1327.​2001.​02185.​x.PubMed
90.
Zurück zum Zitat Yu H, Berkel H. Prostate-specific antigen (PSA) in women. J La State Med Soc. 1999;151(4):209–13.PubMed Yu H, Berkel H. Prostate-specific antigen (PSA) in women. J La State Med Soc. 1999;151(4):209–13.PubMed
91.
Zurück zum Zitat Narita D, Anghel A, Motoc M. Prostate-specific antigen may serve as a pathological predictor in breast cancer. Rom J Morphol Embryol. 2008;49(2):173–80.PubMed Narita D, Anghel A, Motoc M. Prostate-specific antigen may serve as a pathological predictor in breast cancer. Rom J Morphol Embryol. 2008;49(2):173–80.PubMed
92.
Zurück zum Zitat Sauter ER, Daly M, Linahan K, Ehya H, Engstrom PF, Bonney G, et al. Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1996;5(12):967–70.PubMed Sauter ER, Daly M, Linahan K, Ehya H, Engstrom PF, Bonney G, et al. Prostate-specific antigen levels in nipple aspirate fluid correlate with breast cancer risk. Cancer Epidemiol Biomarkers Prev. 1996;5(12):967–70.PubMed
94.
Zurück zum Zitat Sauter ER, Chervoneva I, Diamandis A, Khosravi JM, Litwin S, Diamandis EP. Prostate-specific antigen and insulin-like growth factor binding protein-3 in nipple aspirate fluid are associated with breast cancer. Cancer Detect Prev. 2002;26(2):149–57. doi:10.1016/S0361-090X(02)00028-4.PubMed Sauter ER, Chervoneva I, Diamandis A, Khosravi JM, Litwin S, Diamandis EP. Prostate-specific antigen and insulin-like growth factor binding protein-3 in nipple aspirate fluid are associated with breast cancer. Cancer Detect Prev. 2002;26(2):149–57. doi:10.​1016/​S0361-090X(02)00028-4.PubMed
95.
Zurück zum Zitat Narita D, Cimpean AM, Anghel A, Raica M. Prostate-specific antigen value as a marker in breast cancer. Neoplasma. 2006;53(2):161–7.PubMed Narita D, Cimpean AM, Anghel A, Raica M. Prostate-specific antigen value as a marker in breast cancer. Neoplasma. 2006;53(2):161–7.PubMed
96.
Zurück zum Zitat Yang Q, Nakamura M, Nakamura Y, Yoshimura G, Suzuma T, Umemura T, et al. Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer. Anticancer Res. 2002;22(3):1825–8.PubMed Yang Q, Nakamura M, Nakamura Y, Yoshimura G, Suzuma T, Umemura T, et al. Correlation of prostate-specific antigen promoter polymorphisms with clinicopathological characteristics in breast cancer. Anticancer Res. 2002;22(3):1825–8.PubMed
97.
Zurück zum Zitat Look MP, Foekens JA. Clinical relevance of the urokinase plasminogen activator system in breast cancer. APMIS. 1999;107(1):150–9.PubMed Look MP, Foekens JA. Clinical relevance of the urokinase plasminogen activator system in breast cancer. APMIS. 1999;107(1):150–9.PubMed
98.
Zurück zum Zitat Descotes F, Ville G, Bobin JY, Barbier Y, Saez S. Tissue extraction procedures for investigation of urokinase plasminogen activator (uPA) and its inhibitors PAI-1 and PAI-2 in human breast carcinomas. Breast Cancer Res Treat. 1998;49(2):135–43. doi:10.1023/A:1006015529564.PubMed Descotes F, Ville G, Bobin JY, Barbier Y, Saez S. Tissue extraction procedures for investigation of urokinase plasminogen activator (uPA) and its inhibitors PAI-1 and PAI-2 in human breast carcinomas. Breast Cancer Res Treat. 1998;49(2):135–43. doi:10.​1023/​A:​1006015529564.PubMed
99.
Zurück zum Zitat Hurd TC, Sait S, Kohga S, Winston J, Martinick M, Saxena R, et al. Plasminogen activator system localization in 60 cases of ductal carcinoma in situ. Ann Surg Oncol. 2007;14(11):3117–24. doi:10.1245/s10434-007-9529-y.PubMed Hurd TC, Sait S, Kohga S, Winston J, Martinick M, Saxena R, et al. Plasminogen activator system localization in 60 cases of ductal carcinoma in situ. Ann Surg Oncol. 2007;14(11):3117–24. doi:10.​1245/​s10434-007-9529-y.PubMed
100.
Zurück zum Zitat Annecke K, Schmitt M, Euler U, Zerm M, Paepke D, Paepke S, et al. uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv Clin Chem. 2008;45:31–45. doi:10.1016/S0065-2423(07)00002-9.PubMed Annecke K, Schmitt M, Euler U, Zerm M, Paepke D, Paepke S, et al. uPA and PAI-1 in breast cancer: review of their clinical utility and current validation in the prospective NNBC-3 trial. Adv Clin Chem. 2008;45:31–45. doi:10.​1016/​S0065-2423(07)00002-9.PubMed
101.
Zurück zum Zitat Tyndall JD, Kelso MJ, Clingan P, Ranson M. Peptides and small molecules targeting the plasminogen activation system: towards prophylactic anti-metastasis drugs for breast cancer. Recent Patents Anticancer Drug Discov 2008;3(1):1–13.PubMed Tyndall JD, Kelso MJ, Clingan P, Ranson M. Peptides and small molecules targeting the plasminogen activation system: towards prophylactic anti-metastasis drugs for breast cancer. Recent Patents Anticancer Drug Discov 2008;3(1):1–13.PubMed
102.
Zurück zum Zitat Campbell PG, Durham SK, Suwanichkul A, Hayes JD, Powell DR. Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3. Am J Physiol. 1998;275(2 Pt 1):E321–31.PubMed Campbell PG, Durham SK, Suwanichkul A, Hayes JD, Powell DR. Plasminogen binds the heparin-binding domain of insulin-like growth factor-binding protein-3. Am J Physiol. 1998;275(2 Pt 1):E321–31.PubMed
103.
Zurück zum Zitat Campbell PG, Andress DL. Plasmin degradation of insulin-like growth factor-binding protein-5 (IGFBP-5): regulation by IGFBP-5-(201-218). Am J Physiol. 1997;273(5 Pt 1):E996–1004.PubMed Campbell PG, Andress DL. Plasmin degradation of insulin-like growth factor-binding protein-5 (IGFBP-5): regulation by IGFBP-5-(201-218). Am J Physiol. 1997;273(5 Pt 1):E996–1004.PubMed
104.
105.
Zurück zum Zitat Sorrell AM, Shand JH, Tonner E, Gamberoni M, Accorsi PA, Beattie J, et al. Insulin-like growth factor binding protein-5 activates plasminogen by interaction with tissue plasminogen activator, independently of its ability to bind to plasminogen activator inhibitor-1, insulin-like growth factor-I or heparin. J Biol Chem. 2006;281:10883–9.PubMed Sorrell AM, Shand JH, Tonner E, Gamberoni M, Accorsi PA, Beattie J, et al. Insulin-like growth factor binding protein-5 activates plasminogen by interaction with tissue plasminogen activator, independently of its ability to bind to plasminogen activator inhibitor-1, insulin-like growth factor-I or heparin. J Biol Chem. 2006;281:10883–9.PubMed
106.
Zurück zum Zitat Lalou C, Lassarre C, Binoux M. A proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that fails to bind IGFs inhibits the mitogenic effects of IGF-I and insulin. Endocrinology. 1996;137(8):3206–12. doi:10.1210/en.137.8.3206.PubMed Lalou C, Lassarre C, Binoux M. A proteolytic fragment of insulin-like growth factor (IGF) binding protein-3 that fails to bind IGFs inhibits the mitogenic effects of IGF-I and insulin. Endocrinology. 1996;137(8):3206–12. doi:10.​1210/​en.​137.​8.​3206.PubMed
107.
108.
Zurück zum Zitat De Leon DD, Issa N, Nainani S, Asmerom Y. Reversal of cathepsin D routing modulation in MCF-7 breast cancer cells expressing antisense insulin-like growth factor II (IGF-II). Horm Metab Res. 1999;31(2–3):142–7. doi:10.1055/s-2007-978712.PubMed De Leon DD, Issa N, Nainani S, Asmerom Y. Reversal of cathepsin D routing modulation in MCF-7 breast cancer cells expressing antisense insulin-like growth factor II (IGF-II). Horm Metab Res. 1999;31(2–3):142–7. doi:10.​1055/​s-2007-978712.PubMed
109.
Zurück zum Zitat Mathieu M, Rochefort H, Barenton B, Prebois C, Vignon F. Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II. Mol Endocrinol. 1990;4(9):1327–35.PubMed Mathieu M, Rochefort H, Barenton B, Prebois C, Vignon F. Interactions of cathepsin-D and insulin-like growth factor-II (IGF-II) on the IGF-II/mannose-6-phosphate receptor in human breast cancer cells and possible consequences on mitogenic activity of IGF-II. Mol Endocrinol. 1990;4(9):1327–35.PubMed
110.
Zurück zum Zitat Cappelletti V, Fioravanti L, Miodini P, Di Fronzo G. Modulation of cathepsin-D and pS2 protein levels in human breast cancer cell lines. Tumour Biol. 1996;17(5):290–8.PubMed Cappelletti V, Fioravanti L, Miodini P, Di Fronzo G. Modulation of cathepsin-D and pS2 protein levels in human breast cancer cell lines. Tumour Biol. 1996;17(5):290–8.PubMed
113.
Zurück zum Zitat Jones JI, D’Ercole AJ, Camacho-Hubner C, Clemmons DR. Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: effects on affinity for IGF-I. Proc Natl Acad Sci U S A. 1991;88(17):7481–5. doi:10.1073/pnas.88.17.7481.PubMed Jones JI, D’Ercole AJ, Camacho-Hubner C, Clemmons DR. Phosphorylation of insulin-like growth factor (IGF)-binding protein 1 in cell culture and in vivo: effects on affinity for IGF-I. Proc Natl Acad Sci U S A. 1991;88(17):7481–5. doi:10.​1073/​pnas.​88.​17.​7481.PubMed
114.
Zurück zum Zitat Coverley JA, Martin JL, Baxter RC. The effect of phosphorylation by casein kinase 2 on the activity of insulin-like growth factor-binding protein-3. Endocrinology. 2000;141(2):564–70. doi:10.1210/en.141.2.564.PubMed Coverley JA, Martin JL, Baxter RC. The effect of phosphorylation by casein kinase 2 on the activity of insulin-like growth factor-binding protein-3. Endocrinology. 2000;141(2):564–70. doi:10.​1210/​en.​141.​2.​564.PubMed
115.
Zurück zum Zitat Martin JL, Coverley JA, Pattison ST, Baxter RC. Insulin-like growth factor-binding protein-3 production by MCF-7 breast cancer cells: stimulation by retinoic acid and cyclic adenosine monophosphate and differential effects of estradiol. Endocrinology. 1995;136(3):1219–26. doi:10.1210/en.136.3.1219.PubMed Martin JL, Coverley JA, Pattison ST, Baxter RC. Insulin-like growth factor-binding protein-3 production by MCF-7 breast cancer cells: stimulation by retinoic acid and cyclic adenosine monophosphate and differential effects of estradiol. Endocrinology. 1995;136(3):1219–26. doi:10.​1210/​en.​136.​3.​1219.PubMed
116.
Zurück zum Zitat Silha JV, Sheppard PC, Mishra S, Gui Y, Schwartz J, Dodd JG, et al. Insulin-like growth factor binding protein-3 attenuates prostate tumor growth by IGF-dependent and IGF-independent mechanisms. Endocrinology. 2006;147:2112–21.PubMed Silha JV, Sheppard PC, Mishra S, Gui Y, Schwartz J, Dodd JG, et al. Insulin-like growth factor binding protein-3 attenuates prostate tumor growth by IGF-dependent and IGF-independent mechanisms. Endocrinology. 2006;147:2112–21.PubMed
117.
Zurück zum Zitat Schedlich LJ, Nilsen T, John AP, Jans DA, Baxter RC. Phosphorylation of insulin-like growth factor binding protein-3 by deoxyribonucleic acid-dependent protein kinase reduces ligand binding and enhances nuclear accumulation. Endocrinology. 2003;144(5):1984–93. doi:10.1210/en.2002-220798.PubMed Schedlich LJ, Nilsen T, John AP, Jans DA, Baxter RC. Phosphorylation of insulin-like growth factor binding protein-3 by deoxyribonucleic acid-dependent protein kinase reduces ligand binding and enhances nuclear accumulation. Endocrinology. 2003;144(5):1984–93. doi:10.​1210/​en.​2002-220798.PubMed
118.
Zurück zum Zitat Conover CA. Glycosylation of insulin-like growth factor binding protein-3 (IGFBP-3) is not required for potentiation of IGF-I action: evidence for processing of cell-bound IGFBP-3. Endocrinology. 1991;129(6):3259–68.PubMed Conover CA. Glycosylation of insulin-like growth factor binding protein-3 (IGFBP-3) is not required for potentiation of IGF-I action: evidence for processing of cell-bound IGFBP-3. Endocrinology. 1991;129(6):3259–68.PubMed
119.
Zurück zum Zitat Jones JI, Gockerman A, Busby WH Jr, Camacho-Hubner C, Clemmons DR. Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I. J Cell Biol. 1993;121(3):679–87. doi:10.1083/jcb.121.3.679.PubMed Jones JI, Gockerman A, Busby WH Jr, Camacho-Hubner C, Clemmons DR. Extracellular matrix contains insulin-like growth factor binding protein-5: potentiation of the effects of IGF-I. J Cell Biol. 1993;121(3):679–87. doi:10.​1083/​jcb.​121.​3.​679.PubMed
120.
Zurück zum Zitat Clemmons DR. IGF binding proteins: regulation of cellular actions. Growth Regul. 1992;2(2):80–7.PubMed Clemmons DR. IGF binding proteins: regulation of cellular actions. Growth Regul. 1992;2(2):80–7.PubMed
122.
Zurück zum Zitat Bach LA, Thotakura NR, Rechler MM. Human insulin-like growth factor binding protein-6 is O-glycosylated. Growth Regul. 1993;3(1):59–62.PubMed Bach LA, Thotakura NR, Rechler MM. Human insulin-like growth factor binding protein-6 is O-glycosylated. Growth Regul. 1993;3(1):59–62.PubMed
124.
Zurück zum Zitat Perks CM, McCaig C, Clarke JB, Clemmons DR, Holly JM. A non-IGF binding mutant of IGFBP-3 modulates cell function in breast epithelial cells. Biochem Biophys Res Commun. 2002;294(5):988–94. doi:10.1016/S0006-291X(02)00569-7.PubMed Perks CM, McCaig C, Clarke JB, Clemmons DR, Holly JM. A non-IGF binding mutant of IGFBP-3 modulates cell function in breast epithelial cells. Biochem Biophys Res Commun. 2002;294(5):988–94. doi:10.​1016/​S0006-291X(02)00569-7.PubMed
125.
127.
Zurück zum Zitat Blum WF, Jenne EW, Reppin F, Kietzmann K, Ranke MB, Bierich JR. Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I. Endocrinology. 1989;125(2):766–72.PubMedCrossRef Blum WF, Jenne EW, Reppin F, Kietzmann K, Ranke MB, Bierich JR. Insulin-like growth factor I (IGF-I)-binding protein complex is a better mitogen than free IGF-I. Endocrinology. 1989;125(2):766–72.PubMedCrossRef
128.
Zurück zum Zitat Nickerson T, Huynh H, Pollak M. Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. Biochem Biophys Res Commun. 1997;237(3):690–3. doi:10.1006/bbrc.1997.7089.PubMed Nickerson T, Huynh H, Pollak M. Insulin-like growth factor binding protein-3 induces apoptosis in MCF7 breast cancer cells. Biochem Biophys Res Commun. 1997;237(3):690–3. doi:10.​1006/​bbrc.​1997.​7089.PubMed
129.
Zurück zum Zitat Jerome L, Alami N, Belanger S, Page V, Yu Q, Paterson J, et al. Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates herceptin activity in vivo. Cancer Res. 2006;66(14):7245–52. doi:10.1158/0008-5472.CAN-05-3555.PubMed Jerome L, Alami N, Belanger S, Page V, Yu Q, Paterson J, et al. Recombinant human insulin-like growth factor binding protein 3 inhibits growth of human epidermal growth factor receptor-2-overexpressing breast tumors and potentiates herceptin activity in vivo. Cancer Res. 2006;66(14):7245–52. doi:10.​1158/​0008-5472.​CAN-05-3555.PubMed
130.
Zurück zum Zitat Firth SM, Fanayan S, Benn D, Baxter RC. Development of resistance to insulin-like growth factor binding protein-3 in transfected T47D breast cancer cells. Biochem Biophys Res Commun. 1998;246(2):325–9. doi:10.1006/bbrc.1998.8615.PubMed Firth SM, Fanayan S, Benn D, Baxter RC. Development of resistance to insulin-like growth factor binding protein-3 in transfected T47D breast cancer cells. Biochem Biophys Res Commun. 1998;246(2):325–9. doi:10.​1006/​bbrc.​1998.​8615.PubMed
131.
Zurück zum Zitat Figueroa JA, Sharma J, Jackson JG, McDermott MJ, Hilsenbeck SG, Yee D. Recombinant insulin-like growth factor binding protein-1 inhibits IGF-I, serum, and estrogen-dependent growth of MCF-7 human breast cancer cells. J Cell Physiol. 1993;157(2):229–36. doi:10.1002/jcp.1041570204.PubMed Figueroa JA, Sharma J, Jackson JG, McDermott MJ, Hilsenbeck SG, Yee D. Recombinant insulin-like growth factor binding protein-1 inhibits IGF-I, serum, and estrogen-dependent growth of MCF-7 human breast cancer cells. J Cell Physiol. 1993;157(2):229–36. doi:10.​1002/​jcp.​1041570204.PubMed
132.
Zurück zum Zitat McGuire WL Jr, Jackson JG, Figueroa JA, Shimasaki S, Powell DR, Yee D. Regulation of insulin-like growth factor-binding protein (IGFBP) expression by breast cancer cells: use of IGFBP-1 as an inhibitor of insulin-like growth factor action. J Natl Cancer Inst. 1992;84(17):1336–41. doi:10.1093/jnci/84.17.1336.PubMed McGuire WL Jr, Jackson JG, Figueroa JA, Shimasaki S, Powell DR, Yee D. Regulation of insulin-like growth factor-binding protein (IGFBP) expression by breast cancer cells: use of IGFBP-1 as an inhibitor of insulin-like growth factor action. J Natl Cancer Inst. 1992;84(17):1336–41. doi:10.​1093/​jnci/​84.​17.​1336.PubMed
133.
Zurück zum Zitat Yee D, Jackson JG, Kozelsky TW, Figueroa JA. Insulin-like growth factor binding protein 1 expression inhibits insulin-like growth factor I action in MCF-7 breast cancer cells. Cell Growth Differ. 1994;5(1):73–7.PubMed Yee D, Jackson JG, Kozelsky TW, Figueroa JA. Insulin-like growth factor binding protein 1 expression inhibits insulin-like growth factor I action in MCF-7 breast cancer cells. Cell Growth Differ. 1994;5(1):73–7.PubMed
134.
Zurück zum Zitat Butt AJ, Firth SM, King MA, Baxter RC. Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. J Biol Chem. 2000;275(50):39174–81. doi:10.1074/jbc.M908888199.PubMed Butt AJ, Firth SM, King MA, Baxter RC. Insulin-like growth factor-binding protein-3 modulates expression of Bax and Bcl-2 and potentiates p53-independent radiation-induced apoptosis in human breast cancer cells. J Biol Chem. 2000;275(50):39174–81. doi:10.​1074/​jbc.​M908888199.PubMed
135.
Zurück zum Zitat Collard TJ, Guy M, Butt AJ, Perks CM, Holly JM, Paraskeva C, et al. Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells. Carcinogenesis. 2003;24(3):393–401. doi:10.1093/carcin/24.3.393.PubMed Collard TJ, Guy M, Butt AJ, Perks CM, Holly JM, Paraskeva C, et al. Transcriptional upregulation of the insulin-like growth factor binding protein IGFBP-3 by sodium butyrate increases IGF-independent apoptosis in human colonic adenoma-derived epithelial cells. Carcinogenesis. 2003;24(3):393–401. doi:10.​1093/​carcin/​24.​3.​393.PubMed
136.
Zurück zum Zitat Gill ZP, Perks CM, Newcomb PV, Holly JM. Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem. 1997;272(41):25602–7. doi:10.1074/jbc.272.41.25602.PubMed Gill ZP, Perks CM, Newcomb PV, Holly JM. Insulin-like growth factor-binding protein (IGFBP-3) predisposes breast cancer cells to programmed cell death in a non-IGF-dependent manner. J Biol Chem. 1997;272(41):25602–7. doi:10.​1074/​jbc.​272.​41.​25602.PubMed
139.
Zurück zum Zitat Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995;377(6550):646–9. doi:10.1038/377646a0.PubMed Buckbinder L, Talbott R, Velasco-Miguel S, Takenaka I, Faha B, Seizinger BR, et al. Induction of the growth inhibitor IGF-binding protein 3 by p53. Nature. 1995;377(6550):646–9. doi:10.​1038/​377646a0.PubMed
141.
Zurück zum Zitat Williams AC, Collard TJ, Perks CM, Newcomb P, Moorghen M, Holly JM, et al. Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res. 2000;60(1):22–7.PubMed Williams AC, Collard TJ, Perks CM, Newcomb P, Moorghen M, Holly JM, et al. Increased p53-dependent apoptosis by the insulin-like growth factor binding protein IGFBP-3 in human colonic adenoma-derived cells. Cancer Res. 2000;60(1):22–7.PubMed
143.
Zurück zum Zitat Butt AJ, Dickson KA, Jambazov S, Baxter RC. Enhancement of tumor necrosis factor-alpha-induced growth inhibition by insulin-like growth factor-binding protein-5 (IGFBP-5), but not IGFBP-3 in human breast cancer cells. Endocrinology. 2005;146(7):3113–22. doi:10.1210/en.2004-1408.PubMed Butt AJ, Dickson KA, Jambazov S, Baxter RC. Enhancement of tumor necrosis factor-alpha-induced growth inhibition by insulin-like growth factor-binding protein-5 (IGFBP-5), but not IGFBP-3 in human breast cancer cells. Endocrinology. 2005;146(7):3113–22. doi:10.​1210/​en.​2004-1408.PubMed
144.
Zurück zum Zitat Perks CM, McCaig C, Clarke JB, Clemmons DR, Holly JM. Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast cancer cells. Biochem Biophys Res Commun. 2002;294(5):995–1000. doi:10.1016/S0006-291X(02)00570-3.PubMed Perks CM, McCaig C, Clarke JB, Clemmons DR, Holly JM. Effects of a non-IGF binding mutant of IGFBP-5 on cell death in human breast cancer cells. Biochem Biophys Res Commun. 2002;294(5):995–1000. doi:10.​1016/​S0006-291X(02)00570-3.PubMed
145.
Zurück zum Zitat Martin JL, Jambazov S. Insulin-like growth factor binding protein-3 in extracellular matrix stimulates adhesion of breast epithelial cells and activation of p44/42 mitogen-activated protein kinase. Endocrinology. 2006;147(9):4400–9. doi:10.1210/en.2006-0094.PubMed Martin JL, Jambazov S. Insulin-like growth factor binding protein-3 in extracellular matrix stimulates adhesion of breast epithelial cells and activation of p44/42 mitogen-activated protein kinase. Endocrinology. 2006;147(9):4400–9. doi:10.​1210/​en.​2006-0094.PubMed
146.
Zurück zum Zitat Perks CM, Newcomb PV, Norman MR, Holly JM. Effect of insulin-like growth factor binding protein-1 on integrin signalling and the induction of apoptosis in human breast cancer cells. J Mol Endocrinol. 1999;22(2):141–50. doi:10.1677/jme.0.0220141.PubMed Perks CM, Newcomb PV, Norman MR, Holly JM. Effect of insulin-like growth factor binding protein-1 on integrin signalling and the induction of apoptosis in human breast cancer cells. J Mol Endocrinol. 1999;22(2):141–50. doi:10.​1677/​jme.​0.​0220141.PubMed
147.
Zurück zum Zitat Schutt B, Langkamp M, Ranke M, Elmlinger M. Intracellular signalling of insulin-like growth factor binding protein-2. Growth Horm IGF Res. 2000;10:A30. Abstract 35. Schutt B, Langkamp M, Ranke M, Elmlinger M. Intracellular signalling of insulin-like growth factor binding protein-2. Growth Horm IGF Res. 2000;10:A30. Abstract 35.
148.
Zurück zum Zitat Irving JA, Lala PK. Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1. Exp Cell Res. 1995;217(2):419–27. doi:10.1006/excr.1995.1105.PubMed Irving JA, Lala PK. Functional role of cell surface integrins on human trophoblast cell migration: regulation by TGF-beta, IGF-II, and IGFBP-1. Exp Cell Res. 1995;217(2):419–27. doi:10.​1006/​excr.​1995.​1105.PubMed
150.
Zurück zum Zitat Clemmons DR, Busby WH, Arai T, Nam TJ, Clarke JB, Jones JI, et al. Role of insulin-like growth factor binding proteins in the control of IGF actions. Prog Growth Factor Res. 1995;6(2–4):357–66. doi:10.1016/0955-2235(95)00013-5.PubMed Clemmons DR, Busby WH, Arai T, Nam TJ, Clarke JB, Jones JI, et al. Role of insulin-like growth factor binding proteins in the control of IGF actions. Prog Growth Factor Res. 1995;6(2–4):357–66. doi:10.​1016/​0955-2235(95)00013-5.PubMed
151.
Zurück zum Zitat Jones JI, Gockerman A, Busby WH Jr, Wright G, Clemmons DR. Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. Proc Natl Acad Sci U S A. 1993;90(22):10553–7. doi:10.1073/pnas.90.22.10553.PubMed Jones JI, Gockerman A, Busby WH Jr, Wright G, Clemmons DR. Insulin-like growth factor binding protein 1 stimulates cell migration and binds to the alpha 5 beta 1 integrin by means of its Arg-Gly-Asp sequence. Proc Natl Acad Sci U S A. 1993;90(22):10553–7. doi:10.​1073/​pnas.​90.​22.​10553.PubMed
152.
Zurück zum Zitat Kiepe D, Van Der Pas A, Ciarmatori S, Standker L, Schutt B, Hoeflich A, et al. Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I. Endocrinology. 2008;149(10):4901–11. doi:10.1210/en.2007-1395.PubMed Kiepe D, Van Der Pas A, Ciarmatori S, Standker L, Schutt B, Hoeflich A, et al. Defined carboxy-terminal fragments of insulin-like growth factor (IGF) binding protein-2 exert similar mitogenic activity on cultured rat growth plate chondrocytes as IGF-I. Endocrinology. 2008;149(10):4901–11. doi:10.​1210/​en.​2007-1395.PubMed
153.
Zurück zum Zitat Andress DL. Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor. Am J Physiol. 1998;274(4 Pt 1):E744–50.PubMed Andress DL. Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor. Am J Physiol. 1998;274(4 Pt 1):E744–50.PubMed
154.
Zurück zum Zitat Oh Y, Muller HL, Pham H, Rosenfeld RG. Demonstration of receptors for insulin-like growth factor binding protein-3 on Hs578T human breast cancer cells. J Biol Chem. 1993;268(35):26045–8.PubMed Oh Y, Muller HL, Pham H, Rosenfeld RG. Demonstration of receptors for insulin-like growth factor binding protein-3 on Hs578T human breast cancer cells. J Biol Chem. 1993;268(35):26045–8.PubMed
155.
Zurück zum Zitat Leal SM, Liu Q, Huang SS, Huang JS. The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor. J Biol Chem. 1997;272(33):20572–6. doi:10.1074/jbc.272.33.20572.PubMed Leal SM, Liu Q, Huang SS, Huang JS. The type V transforming growth factor beta receptor is the putative insulin-like growth factor-binding protein 3 receptor. J Biol Chem. 1997;272(33):20572–6. doi:10.​1074/​jbc.​272.​33.​20572.PubMed
156.
Zurück zum Zitat Burrows C, Holly JM, Laurence NJ, Vernon EG, Carter JV, Clark MA, et al. Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes. Endocrinology. 2006;147(7):3484–500. doi:10.1210/en.2006-0005.PubMed Burrows C, Holly JM, Laurence NJ, Vernon EG, Carter JV, Clark MA, et al. Insulin-like growth factor binding protein 3 has opposing actions on malignant and nonmalignant breast epithelial cells that are each reversible and dependent upon cholesterol-stabilized integrin receptor complexes. Endocrinology. 2006;147(7):3484–500. doi:10.​1210/​en.​2006-0005.PubMed
157.
Zurück zum Zitat Gui Y, Murphy LJ. Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma. J Clin Endocrinol Metab. 2001;86(5):2104–10. doi:10.1210/jc.86.5.2104.PubMed Gui Y, Murphy LJ. Insulin-like growth factor (IGF)-binding protein-3 (IGFBP-3) binds to fibronectin (FN): demonstration of IGF-I/IGFBP-3/fn ternary complexes in human plasma. J Clin Endocrinol Metab. 2001;86(5):2104–10. doi:10.​1210/​jc.​86.​5.​2104.PubMed
158.
Zurück zum Zitat Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3. J Biol Chem. 2000;275(24):18574–80. doi:10.1074/jbc.M002172200.PubMed Shi Z, Xu W, Loechel F, Wewer UM, Murphy LJ. ADAM 12, a disintegrin metalloprotease, interacts with insulin-like growth factor-binding protein-3. J Biol Chem. 2000;275(24):18574–80. doi:10.​1074/​jbc.​M002172200.PubMed
159.
Zurück zum Zitat Nam TJ, Busby WH Jr, Rees C, Clemmons DR. Thrombospondin and osteopontin bind to insulin-like growth factor (IGF)-binding protein-5 leading to an alteration in IGF-I-stimulated cell growth. Endocrinology. 2000;141(3):1100–6. doi:10.1210/en.141.3.1100.PubMed Nam TJ, Busby WH Jr, Rees C, Clemmons DR. Thrombospondin and osteopontin bind to insulin-like growth factor (IGF)-binding protein-5 leading to an alteration in IGF-I-stimulated cell growth. Endocrinology. 2000;141(3):1100–6. doi:10.​1210/​en.​141.​3.​1100.PubMed
160.
Zurück zum Zitat Singh B, Charkowicz D, Mascarenhas D. Insulin-like growth factor-independent effects mediated by a C-terminal metal-binding domain of insulin-like growth factor binding protein-3. J Biol Chem. 2004;279(1):477–87. doi:10.1074/jbc.M307322200.PubMed Singh B, Charkowicz D, Mascarenhas D. Insulin-like growth factor-independent effects mediated by a C-terminal metal-binding domain of insulin-like growth factor binding protein-3. J Biol Chem. 2004;279(1):477–87. doi:10.​1074/​jbc.​M307322200.PubMed
161.
Zurück zum Zitat Lee HY, Moon H, Chun KH, Chang YS, Hassan K, Ji L, et al. Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells. J Natl Cancer Inst. 2004;96(20):1536–48.PubMedCrossRef Lee HY, Moon H, Chun KH, Chang YS, Hassan K, Ji L, et al. Effects of insulin-like growth factor binding protein-3 and farnesyltransferase inhibitor SCH66336 on Akt expression and apoptosis in non-small-cell lung cancer cells. J Natl Cancer Inst. 2004;96(20):1536–48.PubMedCrossRef
162.
Zurück zum Zitat McCaig C, Perks C, Holly J. MAP Kinase inhibitor blocks IGF-independent effect of IGFBP-3 on breast epithelial cell survival and cell attachment. Proceedings of the Endocrine Society’s 83rd Annual Meeting 2001;P2:268. McCaig C, Perks C, Holly J. MAP Kinase inhibitor blocks IGF-independent effect of IGFBP-3 on breast epithelial cell survival and cell attachment. Proceedings of the Endocrine Society’s 83rd Annual Meeting 2001;P2:268.
163.
Zurück zum Zitat McCaig C, Perks CM, Holly JM. Signalling pathways involved in the direct effects of IGFBP-5 on breast epithelial cell attachment and survival. J Cell Biochem. 2002;84(4):784–94. doi:10.1002/jcb.10093.PubMed McCaig C, Perks CM, Holly JM. Signalling pathways involved in the direct effects of IGFBP-5 on breast epithelial cell attachment and survival. J Cell Biochem. 2002;84(4):784–94. doi:10.​1002/​jcb.​10093.PubMed
164.
Zurück zum Zitat Firth SM, Ganeshprasad U, Baxter RC. Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3. J Biol Chem. 1998;273(5):2631–8. doi:10.1074/jbc.273.5.2631.PubMed Firth SM, Ganeshprasad U, Baxter RC. Structural determinants of ligand and cell surface binding of insulin-like growth factor-binding protein-3. J Biol Chem. 1998;273(5):2631–8. doi:10.​1074/​jbc.​273.​5.​2631.PubMed
165.
Zurück zum Zitat Yamanaka Y, Fowlkes JL, Wilson EM, Rosenfeld RG, Oh Y. Characterization of insulin-like growth factor binding protein-3 (IGFBP-3) binding to human breast cancer cells: kinetics of IGFBP-3 binding and identification of receptor binding domain on the IGFBP-3 molecule. Endocrinology. 1999;140(3):1319–28. doi:10.1210/en.140.3.1319.PubMed Yamanaka Y, Fowlkes JL, Wilson EM, Rosenfeld RG, Oh Y. Characterization of insulin-like growth factor binding protein-3 (IGFBP-3) binding to human breast cancer cells: kinetics of IGFBP-3 binding and identification of receptor binding domain on the IGFBP-3 molecule. Endocrinology. 1999;140(3):1319–28. doi:10.​1210/​en.​140.​3.​1319.PubMed
166.
Zurück zum Zitat Hollowood AD, Stewart CE, Perks CM, Pell JM, Lai T, Alderson D, et al. Evidence implicating a mid-region sequence of IGFBP-3 in its specific IGF-independent actions. J Cell Biochem. 2002;86(3):583–9. doi:10.1002/jcb.10223.PubMed Hollowood AD, Stewart CE, Perks CM, Pell JM, Lai T, Alderson D, et al. Evidence implicating a mid-region sequence of IGFBP-3 in its specific IGF-independent actions. J Cell Biochem. 2002;86(3):583–9. doi:10.​1002/​jcb.​10223.PubMed
167.
Zurück zum Zitat Schedlich LJ, Young TF, Firth SM, Baxter RC. Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common nuclear transport pathway in T47D human breast carcinoma cells. J Biol Chem. 1998;273(29):18347–52. doi:10.1074/jbc.273.29.18347.PubMed Schedlich LJ, Young TF, Firth SM, Baxter RC. Insulin-like growth factor-binding protein (IGFBP)-3 and IGFBP-5 share a common nuclear transport pathway in T47D human breast carcinoma cells. J Biol Chem. 1998;273(29):18347–52. doi:10.​1074/​jbc.​273.​29.​18347.PubMed
168.
Zurück zum Zitat Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem. 2000;275(43):33607–13. doi:10.1074/jbc.M002547200.PubMed Liu B, Lee HY, Weinzimer SA, Powell DR, Clifford JL, Kurie JM, et al. Direct functional interactions between insulin-like growth factor-binding protein-3 and retinoid X receptor-alpha regulate transcriptional signaling and apoptosis. J Biol Chem. 2000;275(43):33607–13. doi:10.​1074/​jbc.​M002547200.PubMed
169.
Zurück zum Zitat Lee KW, Ma L, Yan X, Liu B, Zhang XK, Cohen P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. J Biol Chem. 2005;280(17):16942–8. doi:10.1074/jbc.M412757200.PubMed Lee KW, Ma L, Yan X, Liu B, Zhang XK, Cohen P. Rapid apoptosis induction by IGFBP-3 involves an insulin-like growth factor-independent nucleomitochondrial translocation of RXRalpha/Nur77. J Biol Chem. 2005;280(17):16942–8. doi:10.​1074/​jbc.​M412757200.PubMed
170.
Zurück zum Zitat Zappala G, Elbi C, Edwards J, Gorenstein J, Rechler MM, Bhattacharyya N. Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha. Endocrinology. 2008;149(4):1802–12. doi:10.1210/en.2007-1315.PubMed Zappala G, Elbi C, Edwards J, Gorenstein J, Rechler MM, Bhattacharyya N. Induction of apoptosis in human prostate cancer cells by insulin-like growth factor binding protein-3 does not require binding to retinoid X receptor-alpha. Endocrinology. 2008;149(4):1802–12. doi:10.​1210/​en.​2007-1315.PubMed
171.
Zurück zum Zitat Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B, et al. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem. 2006;281(34):24588–601. doi:10.1074/jbc.M509463200.PubMed Bhattacharyya N, Pechhold K, Shahjee H, Zappala G, Elbi C, Raaka B, et al. Nonsecreted insulin-like growth factor binding protein-3 (IGFBP-3) can induce apoptosis in human prostate cancer cells by IGF-independent mechanisms without being concentrated in the nucleus. J Biol Chem. 2006;281(34):24588–601. doi:10.​1074/​jbc.​M509463200.PubMed
173.
Zurück zum Zitat Fanayan S, Firth SM, Butt AJ, Baxter RC. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta) and the type II TGF-beta receptor. J Biol Chem. 2000;275(50):39146–51. doi:10.1074/jbc.M006964200.PubMed Fanayan S, Firth SM, Butt AJ, Baxter RC. Growth inhibition by insulin-like growth factor-binding protein-3 in T47D breast cancer cells requires transforming growth factor-beta (TGF-beta) and the type II TGF-beta receptor. J Biol Chem. 2000;275(50):39146–51. doi:10.​1074/​jbc.​M006964200.PubMed
174.
Zurück zum Zitat Fu P, Thompson JA, Bach LA. Promotion of cancer cell migration: an insulin-like growth factor (IGF)-independent action of IGF-binding protein-6. J Biol Chem. 2007;282(31):22298–306. doi:10.1074/jbc.M703066200.PubMed Fu P, Thompson JA, Bach LA. Promotion of cancer cell migration: an insulin-like growth factor (IGF)-independent action of IGF-binding protein-6. J Biol Chem. 2007;282(31):22298–306. doi:10.​1074/​jbc.​M703066200.PubMed
175.
Zurück zum Zitat Yu Q, Banerjee K, Paterson J, Alami N, Shiry L, Leyland-Jones B. Insulin-like growth factor binding protein-3: single-agent and synergistic effects with chemotherapeutic drugs on solid tumor models. In: Proceedings of the AACR, Abstract 755, Washington DC; 2003. p. 172. Yu Q, Banerjee K, Paterson J, Alami N, Shiry L, Leyland-Jones B. Insulin-like growth factor binding protein-3: single-agent and synergistic effects with chemotherapeutic drugs on solid tumor models. In: Proceedings of the AACR, Abstract 755, Washington DC; 2003. p. 172.
176.
Zurück zum Zitat Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis DL, et al. Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer. 2002;38(18):2362–70. doi:10.1016/S0959-8049(02)00210-1.PubMed Ioachim E, Charchanti A, Briasoulis E, Karavasilis V, Tsanou H, Arvanitis DL, et al. Immunohistochemical expression of extracellular matrix components tenascin, fibronectin, collagen type IV and laminin in breast cancer: their prognostic value and role in tumour invasion and progression. Eur J Cancer. 2002;38(18):2362–70. doi:10.​1016/​S0959-8049(02)00210-1.PubMed
177.
Zurück zum Zitat Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104(41):16158–63. doi:10.1073/pnas.0702596104.PubMed Zhou J, Wulfkuhle J, Zhang H, Gu P, Yang Y, Deng J, et al. Activation of the PTEN/mTOR/STAT3 pathway in breast cancer stem-like cells is required for viability and maintenance. Proc Natl Acad Sci U S A. 2007;104(41):16158–63. doi:10.​1073/​pnas.​0702596104.PubMed
178.
Zurück zum Zitat Clark AS, West K, Streicher S, Dennis PA. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 2002;1(9):707–17.PubMed Clark AS, West K, Streicher S, Dennis PA. Constitutive and inducible Akt activity promotes resistance to chemotherapy, trastuzumab, or tamoxifen in breast cancer cells. Mol Cancer Ther. 2002;1(9):707–17.PubMed
179.
Zurück zum Zitat Kalli KR, Krco CJ, Hartmann LC, Goodman K, Maurer MJ, Yu C, et al. An HLA-DR-degenerate epitope pool detects insulin-like growth factor binding protein 2-specific immunity in patients with cancer. Cancer Res. 2008;68(12):4893–901. doi:10.1158/0008-5472.CAN-07-6726.PubMed Kalli KR, Krco CJ, Hartmann LC, Goodman K, Maurer MJ, Yu C, et al. An HLA-DR-degenerate epitope pool detects insulin-like growth factor binding protein 2-specific immunity in patients with cancer. Cancer Res. 2008;68(12):4893–901. doi:10.​1158/​0008-5472.​CAN-07-6726.PubMed
180.
Zurück zum Zitat Zhang X, Yee D. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility. Cancer Res. 2002;62(15):4369–75.PubMed Zhang X, Yee D. Insulin-like growth factor binding protein-1 (IGFBP-1) inhibits breast cancer cell motility. Cancer Res. 2002;62(15):4369–75.PubMed
181.
Zurück zum Zitat Subramanian A, Sharma AK, Banerjee D, Jiang WG, Mokbel K. Evidence for a tumour suppressive function of IGF1-binding proteins in human breast cancer. Anticancer Res. 2007;27(5B):3513–8.PubMed Subramanian A, Sharma AK, Banerjee D, Jiang WG, Mokbel K. Evidence for a tumour suppressive function of IGF1-binding proteins in human breast cancer. Anticancer Res. 2007;27(5B):3513–8.PubMed
Metadaten
Titel
IGF Binding Proteins (IGFBPs) and Regulation of Breast Cancer Biology
verfasst von
Claire M. Perks
Jeff M. P. Holly
Publikationsdatum
01.12.2008
Verlag
Springer US
Erschienen in
Journal of Mammary Gland Biology and Neoplasia / Ausgabe 4/2008
Print ISSN: 1083-3021
Elektronische ISSN: 1573-7039
DOI
https://doi.org/10.1007/s10911-008-9106-4

Weitere Artikel der Ausgabe 4/2008

Journal of Mammary Gland Biology and Neoplasia 4/2008 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.