Skip to main content
Erschienen in: Der Urologe 3/2013

01.03.2013 | Übersichten

„Transforming growth factor β“ im Prostatakarzinom

Zelluläre Wirkungen und molekulare Grundlagen

verfasst von: M.B. Stope, C. Rönnau, T. Schubert, D. Staar, J. Bradl, P. Ziegler, A. Streitbörger, N. Kroeger, U. Zimmermann, R. Walther, M. Burchardt, C. Börgermann

Erschienen in: Die Urologie | Ausgabe 3/2013

Einloggen, um Zugang zu erhalten

Zusammenfassung

Der pleiotrope Wachstumsfaktor „transforming growth factor β“ (TGF-β) ist in diverse Signalwege involviert und kann eine Vielzahl von Zellantworten beeinflussen. Bei Entstehung und Karzinogenese des Prostatakarzinoms (PCa) können dies sowohl antionkogene Mechanismen (Wachstumshemmung, Apoptose) als auch proonkogene Prozesse sein (Proliferation, Zellbeweglichkeit, Modulierung der Tumorumgebung). Die ursprünglich antiproliferative Wirkung von TGF-β wird dabei im Verlauf der Tumorprogression immer mehr von proonkogenen Effekten überlagert, die häufig durch die Interaktion mit proliferativen Signalkaskaden wie „Mitogen-activated protein-kinase-“ (MAP-Kinase-) oder Androgenrezeptor- (AR-)Signalwegen vermittelt werden. Obgleich TGF-β ein wichtiger Modulator der PCa-Progression ist, sind die zugrundeliegenden molekular-pathologischen Prozesse bisher nur unvollständig verstanden.
Literatur
1.
Zurück zum Zitat Ahamed J, Burg N, Yoshinaga K et al (2008) In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1. Blood 112:3650–3660PubMedCrossRef Ahamed J, Burg N, Yoshinaga K et al (2008) In vitro and in vivo evidence for shear-induced activation of latent transforming growth factor-β1. Blood 112:3650–3660PubMedCrossRef
2.
Zurück zum Zitat Ajiboye S, Sissung TM, Sharifi N et al (2010) More than an accessory: implications of type III transforming growth factor-β receptor loss in prostate cancer. BJU Int 105:913–916PubMedCrossRef Ajiboye S, Sissung TM, Sharifi N et al (2010) More than an accessory: implications of type III transforming growth factor-β receptor loss in prostate cancer. BJU Int 105:913–916PubMedCrossRef
3.
Zurück zum Zitat Arjaans M, Oude Munnink TH, Timmer-Bosscha H et al (2012) Transforming growth factor (TGF)-β expression and activation mechanisms as potential targets for anti-tumor therapy and tumor imaging. Pharmacol Ther 135:123–132PubMedCrossRef Arjaans M, Oude Munnink TH, Timmer-Bosscha H et al (2012) Transforming growth factor (TGF)-β expression and activation mechanisms as potential targets for anti-tumor therapy and tumor imaging. Pharmacol Ther 135:123–132PubMedCrossRef
4.
Zurück zum Zitat Bruckheimer EM, Kyprianou N (2001) Dihydrotestosterone enhances transforming growth factor-β-induced apoptosis in hormone-sensitive prostate cancer cells. Endocrinol 142:2419–2426CrossRef Bruckheimer EM, Kyprianou N (2001) Dihydrotestosterone enhances transforming growth factor-β-induced apoptosis in hormone-sensitive prostate cancer cells. Endocrinol 142:2419–2426CrossRef
5.
Zurück zum Zitat Danielpour D (2005) Functions and regulation of transforming growth factor-beta (TGF-β) in the prostate. Eur J Cancer 41:846–857PubMedCrossRef Danielpour D (2005) Functions and regulation of transforming growth factor-beta (TGF-β) in the prostate. Eur J Cancer 41:846–857PubMedCrossRef
6.
Zurück zum Zitat Di K, Ling MT, Tsao SW et al (2006) Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. Biol Cell 98:523–533PubMedCrossRef Di K, Ling MT, Tsao SW et al (2006) Id-1 modulates senescence and TGF-β1 sensitivity in prostate epithelial cells. Biol Cell 98:523–533PubMedCrossRef
7.
Zurück zum Zitat Di K, Wong YC, Wang X (2007) Id-1 promotes TGF-beta1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells. Exp Cell Res 313:3983–3999PubMedCrossRef Di K, Wong YC, Wang X (2007) Id-1 promotes TGF-beta1-induced cell motility through HSP27 activation and disassembly of adherens junction in prostate epithelial cells. Exp Cell Res 313:3983–3999PubMedCrossRef
8.
Zurück zum Zitat Diener KR, Need NF, Buchanan G et al (2010) TGF-beta signalling and immunity in prostate tumourigenesis. Expert Opin Ther Targets 14:179–192PubMedCrossRef Diener KR, Need NF, Buchanan G et al (2010) TGF-beta signalling and immunity in prostate tumourigenesis. Expert Opin Ther Targets 14:179–192PubMedCrossRef
9.
Zurück zum Zitat Edlund S, Bu S, Schuster N et al (2003) Transforming growth factor-β1 (TGF-β)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-β-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell 14:529–544PubMedCrossRef Edlund S, Bu S, Schuster N et al (2003) Transforming growth factor-β1 (TGF-β)-induced apoptosis of prostate cancer cells involves Smad7-dependent activation of p38 by TGF-β-activated kinase 1 and mitogen-activated protein kinase kinase 3. Mol Biol Cell 14:529–544PubMedCrossRef
10.
Zurück zum Zitat Festuccia C, Bologna M, Gravina GL et al (1999) Osteoblast conditioned media contain TGF-beta1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer 81:395–403PubMedCrossRef Festuccia C, Bologna M, Gravina GL et al (1999) Osteoblast conditioned media contain TGF-beta1 and modulate the migration of prostate tumor cells and their interactions with extracellular matrix components. Int J Cancer 81:395–403PubMedCrossRef
11.
Zurück zum Zitat Huang X, Chen S, Xu L et al (2005) Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Res 65:3470–3478PubMed Huang X, Chen S, Xu L et al (2005) Genistein inhibits p38 map kinase activation, matrix metalloproteinase type 2, and cell invasion in human prostate epithelial cells. Cancer Res 65:3470–3478PubMed
12.
Zurück zum Zitat Joffroy CM, Buck MB, Stope MB et al (2010) Antiestrogens induce transforming growth factor β-mediated immunosuppression in breast cancer. Cancer Res 70:1314–1322PubMedCrossRef Joffroy CM, Buck MB, Stope MB et al (2010) Antiestrogens induce transforming growth factor β-mediated immunosuppression in breast cancer. Cancer Res 70:1314–1322PubMedCrossRef
13.
Zurück zum Zitat Kang HY, Huang KE, Chang SY et al (2002) Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4. J Biol Chem 277:43749–43756PubMedCrossRef Kang HY, Huang KE, Chang SY et al (2002) Differential modulation of androgen receptor-mediated transactivation by Smad3 and tumor suppressor Smad4. J Biol Chem 277:43749–43756PubMedCrossRef
14.
Zurück zum Zitat Konrad L, Schreiber JA, Schwarz L et al (2009) TGF-β1 and TGF-β2 strongly enhance the secretion of plasminogen activator inhibitor-1 and matrix metalloproteinase-9 of the human prostate cancer cell line PC-3. Regul Pept 155:28–32PubMedCrossRef Konrad L, Schreiber JA, Schwarz L et al (2009) TGF-β1 and TGF-β2 strongly enhance the secretion of plasminogen activator inhibitor-1 and matrix metalloproteinase-9 of the human prostate cancer cell line PC-3. Regul Pept 155:28–32PubMedCrossRef
15.
Zurück zum Zitat Lamm MLG, Long DD, Goodwin SM et al (1997) Transforming growth factor-β1 inhibits membrane association of protein kinase Cα in a human prostate cancer cell line, PC3. Endocrinol 138:4657–4664CrossRef Lamm MLG, Long DD, Goodwin SM et al (1997) Transforming growth factor-β1 inhibits membrane association of protein kinase Cα in a human prostate cancer cell line, PC3. Endocrinol 138:4657–4664CrossRef
16.
Zurück zum Zitat Le Brun G, Aubin P, Soliman H et al (1998) Upregulation of endothelin 1 and its precursor by IL-1β, TNF-α, and TGF-β in the PC3 human prostate cancer cell line. Cytokine 11:157–162 Le Brun G, Aubin P, Soliman H et al (1998) Upregulation of endothelin 1 and its precursor by IL-1β, TNF-α, and TGF-β in the PC3 human prostate cancer cell line. Cytokine 11:157–162
17.
Zurück zum Zitat Lecanda J, Parekh TV, Gama P et al (2007) Transforming growth factor-β, estrogen, and progesterone converge on the regulation of p27Kip1 in the normal and malignant endometrium. Cancer Res 67:1007–1018PubMedCrossRef Lecanda J, Parekh TV, Gama P et al (2007) Transforming growth factor-β, estrogen, and progesterone converge on the regulation of p27Kip1 in the normal and malignant endometrium. Cancer Res 67:1007–1018PubMedCrossRef
18.
Zurück zum Zitat Li X, Placencio V, Iturregui JM et al (2008) Prostate tumor progression is mediated by a paracrine TGF-β/Wnt3a signaling axis. Oncogene 27:7118–7130PubMedCrossRef Li X, Placencio V, Iturregui JM et al (2008) Prostate tumor progression is mediated by a paracrine TGF-β/Wnt3a signaling axis. Oncogene 27:7118–7130PubMedCrossRef
19.
Zurück zum Zitat Lu S, Dong Z. (2006) Characterization of TGF-β-regulated interleukin-8 expression in human prostate cancer cells. Prostate 66:996–1004PubMedCrossRef Lu S, Dong Z. (2006) Characterization of TGF-β-regulated interleukin-8 expression in human prostate cancer cells. Prostate 66:996–1004PubMedCrossRef
20.
21.
Zurück zum Zitat Noda D, Itoh S, Watanabe Y et al (2006) ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-β/Smad-induced growth arrest of prostate cells. Oncogene 25:5591–5500PubMedCrossRef Noda D, Itoh S, Watanabe Y et al (2006) ELAC2, a putative prostate cancer susceptibility gene product, potentiates TGF-β/Smad-induced growth arrest of prostate cells. Oncogene 25:5591–5500PubMedCrossRef
22.
Zurück zum Zitat Park B-J, Park J-I, Byun D-S et al (2000) Mitogenic conversion of transforming growth factor-β1 effect by oncogenic Ha-Ras-induced activation of the mitogen-activated protein kinase signaling pathway in human prostate cancer. Cancer Res 60:3031–3038PubMed Park B-J, Park J-I, Byun D-S et al (2000) Mitogenic conversion of transforming growth factor-β1 effect by oncogenic Ha-Ras-induced activation of the mitogen-activated protein kinase signaling pathway in human prostate cancer. Cancer Res 60:3031–3038PubMed
23.
Zurück zum Zitat Park J-I, Lee M-G, Cho K et al (2003) Transforming growth factor-β1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene 22:4314–4332PubMedCrossRef Park J-I, Lee M-G, Cho K et al (2003) Transforming growth factor-β1 activates interleukin-6 expression in prostate cancer cells through the synergistic collaboration of the Smad2, p38-NF-kappaB, JNK, and Ras signaling pathways. Oncogene 22:4314–4332PubMedCrossRef
24.
Zurück zum Zitat Perry KT, Anthony CT, Steiner MS (1997) Immunohistochemical localization of TGF β1, TGF β 2, and TGF β 3 in normal and malignant human prostate. Prostate 33:133–140PubMedCrossRef Perry KT, Anthony CT, Steiner MS (1997) Immunohistochemical localization of TGF β1, TGF β 2, and TGF β 3 in normal and malignant human prostate. Prostate 33:133–140PubMedCrossRef
25.
Zurück zum Zitat Reis ST, Pontes-Junior J, Antunes AA et al (2011) Tgf- β 1 expression as a biomarker of poor prognosis in prostate cancer. Clinics 66:1143–1147PubMed Reis ST, Pontes-Junior J, Antunes AA et al (2011) Tgf- β 1 expression as a biomarker of poor prognosis in prostate cancer. Clinics 66:1143–1147PubMed
26.
Zurück zum Zitat Sakko AJ, Ricciardelli C, Mayne K et al (2001) Versican accumulation in human prostatic fibroblast cultures is enhanced by prostate cancer cell-derived transforming growth factor beta1. Cancer Res 61:926–930PubMed Sakko AJ, Ricciardelli C, Mayne K et al (2001) Versican accumulation in human prostatic fibroblast cultures is enhanced by prostate cancer cell-derived transforming growth factor beta1. Cancer Res 61:926–930PubMed
27.
Zurück zum Zitat Sehgal I, Thompson TC (1999) Novel regulation of type IV collagenase (matrix metalloproteinase-9 and −2) activities by transforming growth factor- β1 in human prostate cancer cell lines. Mol Biol Cell 10:407–416PubMed Sehgal I, Thompson TC (1999) Novel regulation of type IV collagenase (matrix metalloproteinase-9 and −2) activities by transforming growth factor- β1 in human prostate cancer cell lines. Mol Biol Cell 10:407–416PubMed
28.
Zurück zum Zitat Sintich SM, Lamm MLG, Sensibar JA et al (1999) Transforming growth factor-β1-induced proliferation of the prostate cancer cell line, TSU-Pr1: The role of platelet-derived growth factor. Endocrinol 140:3411–3415CrossRef Sintich SM, Lamm MLG, Sensibar JA et al (1999) Transforming growth factor-β1-induced proliferation of the prostate cancer cell line, TSU-Pr1: The role of platelet-derived growth factor. Endocrinol 140:3411–3415CrossRef
29.
Zurück zum Zitat Steiner MS, Wand GS, Barrack ER (1994) Effects of transforming growth factor β1 on the adenylyl cyclase-cAMP pathway in prostate cancer. Growth Factors 11:283–290PubMedCrossRef Steiner MS, Wand GS, Barrack ER (1994) Effects of transforming growth factor β1 on the adenylyl cyclase-cAMP pathway in prostate cancer. Growth Factors 11:283–290PubMedCrossRef
30.
Zurück zum Zitat Stope MB, Popp SL, Knabbe C et al (2010) Estrogen receptor alpha attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands. Breast Cancer Res Treat 120:357–367PubMedCrossRef Stope MB, Popp SL, Knabbe C et al (2010) Estrogen receptor alpha attenuates transforming growth factor-β signaling in breast cancer cells independent from agonistic and antagonistic ligands. Breast Cancer Res Treat 120:357–367PubMedCrossRef
31.
Zurück zum Zitat Stope MB, Schubert T, Staar D et al (2012) Effect of the heat shock protein HSP27 on androgen receptor expression and function in prostate cancer cells. World J Urol 30:327–331PubMedCrossRef Stope MB, Schubert T, Staar D et al (2012) Effect of the heat shock protein HSP27 on androgen receptor expression and function in prostate cancer cells. World J Urol 30:327–331PubMedCrossRef
32.
Zurück zum Zitat Unlü A, Leake RE (2003) Transforming growth factor β1 stimulates urokinase plasminogen activator system on prostate cancer cells. Int J Biol Markers 18:147–151PubMed Unlü A, Leake RE (2003) Transforming growth factor β1 stimulates urokinase plasminogen activator system on prostate cancer cells. Int J Biol Markers 18:147–151PubMed
33.
Zurück zum Zitat Weydert CJ, Esser AK, Mejia RA et al (2009) Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles. Cancer Biol Ther 8:720–729PubMedCrossRef Weydert CJ, Esser AK, Mejia RA et al (2009) Endothelin-1 inhibits prostate cancer growth in vivo through vasoconstriction of tumor-feeding arterioles. Cancer Biol Ther 8:720–729PubMedCrossRef
34.
Zurück zum Zitat Xu L, Chen S, Bergan RC (2006) MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene 25:2987–2998PubMedCrossRef Xu L, Chen S, Bergan RC (2006) MAPKAPK2 and HSP27 are downstream effectors of p38 MAP kinase-mediated matrix metalloproteinase type 2 activation and cell invasion in human prostate cancer. Oncogene 25:2987–2998PubMedCrossRef
35.
Zurück zum Zitat Yang F, Strand DW, Rowley DR (2008) Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma. Oncogene 27:450–459PubMedCrossRef Yang F, Strand DW, Rowley DR (2008) Fibroblast growth factor-2 mediates transforming growth factor-β action in prostate cancer reactive stroma. Oncogene 27:450–459PubMedCrossRef
36.
Zurück zum Zitat Zhu B, Fukada K, Zhu H et al (2006) Prohibitin and cofilin are intracellular effectors of transforming growth factor β signaling in human prostate cancer cells. Cancer Res 66:8640–8647PubMedCrossRef Zhu B, Fukada K, Zhu H et al (2006) Prohibitin and cofilin are intracellular effectors of transforming growth factor β signaling in human prostate cancer cells. Cancer Res 66:8640–8647PubMedCrossRef
Metadaten
Titel
„Transforming growth factor β“ im Prostatakarzinom
Zelluläre Wirkungen und molekulare Grundlagen
verfasst von
M.B. Stope
C. Rönnau
T. Schubert
D. Staar
J. Bradl
P. Ziegler
A. Streitbörger
N. Kroeger
U. Zimmermann
R. Walther
M. Burchardt
C. Börgermann
Publikationsdatum
01.03.2013
Verlag
Springer-Verlag
Erschienen in
Die Urologie / Ausgabe 3/2013
Print ISSN: 2731-7064
Elektronische ISSN: 2731-7072
DOI
https://doi.org/10.1007/s00120-012-3049-5

Weitere Artikel der Ausgabe 3/2013

Der Urologe 3/2013 Zur Ausgabe

Mitteilungen der DGU

Termine

URO-Telegramm

URO-Telegramm

Berufspolitik BDU

Berufspolitik BDU

Update Urologie

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