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Journal of Mammary Gland Biology and Neoplasia

Erschienen in:

01.03.2008

Jak2/Stat5 Signaling in Mammogenesis, Breast Cancer Initiation and Progression

verfasst von: Kay-Uwe Wagner, Hallgeir Rui

Erschienen in: Journal of Mammary Gland Biology and Neoplasia | Ausgabe 1/2008

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Abstract

During normal mammary gland development, the tyrosine kinase Jak2 and its main substrate, the signal transducer and activator of transcription-5 (Stat5), are critical for the growth and differentiation of alveolar progenitors as well as the survival of secretory mammary epithelial cells. Genetic studies in mouse models support a role for the Stat5 transcription factor as a proto-oncogene in mammary tumor initiation. On the other hand, the analysis of nuclear Stat5 in human breast malignancies suggests a role of the Jak2/Stat5 pathway in the restriction of the metastatic potential of neoplastic mammary epithelial cells. Following an overview on the function of the Jak2/Stat5 pathway during normal mammary gland development, this review discusses recently published observations on human breast cancers as well as experimental evidence from genetically engineered mice that propose a dual role of Jak2/Stat5 signaling in breast cancer initiation and progression. Future studies to further test the concept of contrasting effects of Jak2/Stat5 pathway on breast cancer initiation and metastatic progression are proposed.

Aaronson DS, Horvath CM. A road map for those who don’t know JAK-STAT. Science. 2002;296(5573):1653–5.PubMed

Kisseleva T, Bhattacharya S, Braunstein J, Schindler CW. Signaling through the JAK/STAT pathway, recent advances and future challenges. Gene. 2002;285(1–2):1–24.PubMed

Ihle JN. The Stat family in cytokine signaling. Curr Opin Cell Biol. 2001;13(2):211–7.PubMed

Levy DE, Darnell JE Jr. Stats: transcriptional control and biological impact. Nat Rev Mol Cell Biol. 2002;3(9):651–62.PubMed

Rui H, Kirken RA, Farrar WL. Activation of receptor-associated tyrosine kinase JAK2 by prolactin. J Biol Chem. 1994;269(7):5364–8.PubMed

DaSilva L, Howard OM, Rui H, Kirken RA, Farrar WL. Growth signaling and JAK2 association mediated by membrane-proximal cytoplasmic regions of prolactin receptors. J Biol Chem. 1994;269(28):18267–70.PubMed

Sakamoto K, Creamer BA, Triplett AA, Wagner KU. The Janus kinase 2 is required for expression and nuclear accumulation of Cyclin D1 in proliferating mammary epithelial cells. Mol Endocrinol. 2007;21(8):1877–92.PubMed

Wakao H, Gouilleux F, Groner B. Mammary gland factor (MGF) is a novel member of the cytokine regulated transcription factor gene family and confers the prolactin response [published erratum appears in EMBO J 1995 Feb 15;14(4):854–5]. EMBO J. 1994;13(9):2182–91.PubMed

Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc Natl Acad Sci USA 1995;92(19):8831–5.PubMed

10.

Nevalainen MT, Xie J, Bubendorf L, Wagner KU, Rui H. Basal activation of transcription factor signal transducer and activator of transcription (Stat5) in nonpregnant mouse and human breast epithelium. Mol Endocrinol. 2002;16(5):1108–24.PubMed

11.

Wagner KU, Krempler A, Triplett AA, Qi Y, George NM, Zhu J, et al. Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. Mol Cell Biol. 2004;24(12):5510–20.PubMed

12.

Liu X, Robinson GW, Hennighausen L. Activation of Stat5a and Stat5b by tyrosine phosphorylation is tightly linked to mammary gland differentiation. Mol Endocrinol. 1996;10(12):1496–506.PubMed

13.

Cui Y, Riedlinger G, Miyoshi K, Tang W, Li C, Deng CX, et al. Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol Cell Biol. 2004;24(18):8037–47.PubMed

14.

Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 1997;11(2):179–86.PubMed

15.

Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, et al. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell. 1998;93:841–50.PubMed

16.

LeBaron MJ, Ahonen TJ, Nevalainen MT, Rui H. In vivo response-based identification of direct hormone target cell populations using high-density tissue arrays. Endocrinology. 2007;148(3):989–1008.PubMed

17.

Jones FE, Welte T, Fu XY, Stern DF. ErbB4 signaling in the mammary gland is required for lobuloalveolar development and Stat5 activation during lactation. J Cell Biol. 1999;147(1):77–88.PubMed

18.

Kazansky AV, Kabotyanski EB, Wyszomierski SL, Mancini MA, Rosen JM. Differential effects of prolactin and src/abl kinases on the nuclear translocation of STAT5B and STAT5A. J Biol Chem. 1999;274(32):22484–92.PubMed

19.

Neilson LM, Zhu J, Xie J, Malabarba MG, Sakamoto K, Wagner KU, Kirken RA, Rui H. Coactivation of janus tyrosine kinase (Jak)1 positively modulates prolactin-Jak2 signaling in breast cancer: recruitment of ERK and signal transducer and activator of transcription (Stat)3 and enhancement of Akt and Stat5a/b pathways. Mol Endocrinol. 2007;21(9):2218–32.

20.

Horseman ND, Zhao W, Montecino-Rodriguez E, Tanaka M, Nakashima K, Engle SJ, et al. Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J. 1997;16:6926–35.PubMed

21.

Ormandy CJ, Camus A, Barra J, Damotte D, Lucas B, Buteau H, et al. Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev. 1997;11(2):167–78.PubMed

22.

Brisken C, Kaur S, Chavarria TE, Binart N, Sutherland RL, Weinberg RA, et al. Prolactin controls mammary gland development via direct and indirect mechanisms. Dev Biol. 1999;210(1):96–106.PubMed

23.

Miyoshi K, Shillingford JM, Smith GH, Grimm SL, Wagner KU, Oka T, et al. Signal transducer and activator of transcription (Stat) 5 controls the proliferation and differentiation of mammary alveolar epithelium. J Cell Biol. 2001;155(4):531–42.PubMed

24.

Hennighausen L, Robinson GW, Wagner KU, Liu W. Prolactin signaling in mammary gland development. J Biol Chem. 1997;272(12):7567–9.PubMed

25.

Das R, Vonderhaar BK. Prolactin as a mitogen in mammary cells. J Mammary Gland Biol Neoplasia. 1997;2(1):29–39.PubMed

26.

Erwin RA, Kirken RA, Malabarba MG, Farrar WL, Rui H. Prolactin activates Ras via signaling proteins SHC, growth factor receptor bound 2, and son of sevenless. Endocrinology. 1995;136(8):3512–8.PubMed

27.

Grimley PM, Dong F, Rui H. Stat5a and Stat5b: fraternal twins of signal transduction and transcriptional activation. Cytokine Growth Factor Rev. 1999;10(2):131–57.PubMed

28.

Llovera M, Touraine P, Kelly PA, Goffin V. Involvement of prolactin in breast cancer: redefining the molecular targets. Exp Gerontol. 2000;35(1):41–51.PubMed

29.

Liu X, Gallego MI, Smith GH, Robinson GW, Hennighausen L. Functional rescue of Stat5a-null mammary tissue through the activation of compensating signals including Stat5b. Cell Growth Differ. 1998;9(9):795–803.PubMed

30.

Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, et al. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc Natl Acad Sci USA 1997;94(14):7239–44.PubMed

31.

Gallego MI, Binart N, Robinson GW, Okagaki R, Coschigano KT, Perry J, et al. Prolactin, growth hormone, and epidermal growth factor activate Stat5 in different compartments of mammary tissue and exert different and overlapping developmental effects. Dev Biol. 2001;229(1):163–75.PubMed

32.

Bunting KD, Bradley HL, Hawley TS, Moriggl R, Sorrentino BP, Ihle JN. Reduced lymphomyeloid repopulating activity from adult bone marrow and fetal liver of mice lacking expression of STAT5. Blood. 2002;99(2):479–87.PubMed

33.

Kieslinger M, Woldman I, Moriggl R, Hofmann J, Marine JC, Ihle JN, et al. Antiapoptotic activity of Stat5 required during terminal stages of myeloid differentiation. Genes Dev. 2000;14(2):232–44.PubMed

34.

Moriggl R, Topham DJ, Teglund S, Sexl V, McKay C, Wang D, et al. Stat5 is required for IL-2-induced cell cycle progression of peripheral T cells. Immunity. 1999;10(2):249–59.PubMed

35.

Parganas E, Wang D, Stravopodis D, Topham DJ, Marine JC, Teglund S, et al. Jak2 is essential for signaling through a variety of cytokine receptors. Cell. 1998;93:385–95.PubMed

36.

Neubauer H, Cumano A, Muller M, Wu H, Huffstadt U, Pfeffer K. Jak2 deficiency defines an essential developmental checkpoint in definitive hematopoiesis. Cell. 1998;93:397–409.PubMed

37.

Zhao L, Hart S, Cheng J, Melenhorst JJ, Bierie B, Ernst M, et al. Mammary gland remodeling depends on gp130 signaling through Stat3 and MAPK. J Biol Chem. 2004;279(42):44093–100.PubMed

38.

Shillingford JM, Miyoshi K, Robinson GW, Grimm SL, Rosen JM, Neubauer H, et al. Jak2 is an essential tyrosine kinase involved in pregnancy-mediated development of mammary secretory epithelium. Mol Endocrinol. 2002;16(3):563–70.PubMed

39.

Krempler A, Qi Y, Triplett AA, Zhu J, Rui H, Wagner KU. Generation of a conditional knockout allele for the Janus kinase 2 (Jak2) gene in mice. Genesis. 2004;40(1):52–7.PubMed

40.

Iavnilovitch E, Groner B, Barash I. Overexpression and forced activation of stat5 in mammary gland of transgenic mice promotes cellular proliferation, enhances differentiation, and delays postlactational apoptosis. Mol Cancer Res 2002;1(1):32–47.PubMed

41.

Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, et al. Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc Natl Acad Sci USA 1997;94(7):3425–30.PubMed

42.

Cardiff RD. Are the TDLU of the human the same as the LA of mice? J Mammary Gland Biol Neoplasia 1998;3(1):3–5.PubMed

43.

Wellings SR, Jensen HM, Marcum RG. An atlas of subgross pathology of the human breast with special reference to possible precancerous lesions. J Natl Cancer Inst. 1975;55(2):231–73.PubMed

44.

Hanahan D, Weinberg RA. The hallmarks of cancer. Cell 2000;100(1):57–70.PubMed

45.

Cotarla I, Ren S, Zhang Y, Gehan E, Singh B, Furth PA. Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers. Int J Cancer. 2004;108(5):665–71.PubMed

46.

Li T, Sotgia F, Vuolo MA, Li M, Yang WC, Pestell RG, et al. Caveolin-1 mutations in human breast cancer: functional association with estrogen receptor alpha-positive status. Am J Pathol 2006;168(6):1998–2013.PubMed

47.

Park DS, Lee H, Frank PG, Razani B, Nguyen AV, Parlow AF, et al. Caveolin-1-deficient mice show accelerated mammary gland development during pregnancy, premature lactation, and hyperactivation of the Jak-2/STAT5a signaling cascade. Mol Biol Cell. 2002;13(10):3416–30.PubMed

48.

Sloan EK, Stanley KL, Anderson RL. Caveolin-1 inhibits breast cancer growth and metastasis. Oncogene 2004;23:7893–7.PubMed

49.

Li J, Hassan GS, Williams TM, Minetti C, Pestell RG, Tanowitz HB, et al. Loss of caveolin-1 causes the hyper-proliferation of intestinal crypt stem cells, with increased sensitivity to whole body gamma-radiation. Cell Cycle. 2005;4(12):1817–25.PubMed

50.

Sotgia F, Schubert W, Pestell RG, Lisanti MP. Genetic ablation of caveolin-1 in mammary epithelial cells increases milk production and hyper-activates STAT5a signaling. Cancer Biol Ther. 2006;5(3):292–7.PubMedCrossRef

51.

Sotgia F, Williams TM, Schubert W, Medina F, Minetti C, Pestell RG, et al. Caveolin-1 deficiency (−/−) conveys premalignant alterations in mammary epithelia, with abnormal lumen formation, growth factor independence, and cell invasiveness. Am J Pathol. 2006;168(1):292–309.PubMed

52.

Williams TM, Cheung MW, Park DS, Razani B, Cohen AW, Muller WJ, et al. Loss of caveolin-1 gene expression accelerates the development of dysplastic mammary lesions in tumor-prone transgenic mice. Mol Biol Cell. 2003;14(3):1027–42.PubMed

53.

Iavnilovitch E, Cardiff RD, Groner B, Barash I. Deregulation of Stat5 expression and activation causes mammary tumors in transgenic mice. Int J Cancer. 2004;112(4):607–19.PubMed

54.

Yamashita H, Iwase H, Toyama T, Fujii Y. Naturally occurring dominant-negative Stat5 suppresses transcriptional activity of estrogen receptors and induces apoptosis in T47D breast cancer cells. Oncogene. 2003;22(11):1638–52.PubMed

55.

Mahler JF, Stokes W, Mann PC, Takaoka M, Maronpot RR. Spontaneous lesions in aging FVB/N mice. Toxicol Pathol. 1996;24(6):710–6.PubMedCrossRef

56.

Nieto AI, Shyamala G, Galvez JJ, Thordarson G, Wakefield LM, Cardiff RD. Persistent mammary hyperplasia in FVB/N mice. Comp Med. 2003;53(4):433–8.PubMed

57.

Wakefield LM, Thordarson G, Nieto AI, Shyamala G, Galvez JJ, Anver MR, et al. Spontaneous pituitary abnormalities and mammary hyperplasia in FVB/NCr mice: implications for mouse modeling. Comp Med. 2003;53(4):424–32.PubMed

58.

Eilon T, Groner B, Barash I. Tumors caused by overexpression and forced activation of Stat5 in mammary epithelial cells of transgenic mice are parity-dependent and developed in aged, postestropausal females. Int J Cancer. 2007;121(9):1892–902.PubMed

59.

Ginger MR, Gonzalez-Rimbau MF, Gay JP, Rosen JM. Persistent changes in gene expression induced by estrogen and progesterone in the rat mammary gland. Mol Endocrinol. 2001;15(11):1993–2009.PubMed

60.

Wagner KU, Smith GH. Pregnancy and stem cell behavior. J Mammary Gland Biol Neoplasia. 2005;10(1):25–36.PubMed

61.

Boulanger CA, Wagner KU, Smith GH. Parity-induced mouse mammary epithelial cells are pluripotent, self-renewing and sensitive to TGF-beta1 expression. Oncogene. 2005;24(4):552–60.PubMed

62.

Matulka LA, Triplett AA, Wagner KU. Parity-induced mammary epithelial cells are multipotent and express cell surface markers associated with stem cells. Dev Biol. 2007;303(1):29–44.PubMed

63.

Wagner KU, Boulanger CA, Henry MD, Sgagias M, Hennighausen L, Smith GH. An adjunct mammary epithelial cell population in parous females: its role in functional adaptation and tissue renewal. Development. 2002;129(6):1377–86.PubMed

64.

Henry MD, Triplett AA, Oh KB, Smith GH, Wagner KU. Parity-induced mammary epithelial cells facilitate tumorigenesis in MMTV-neu transgenic mice. Oncogene. 2004;23(41):6980–5.PubMed

65.

Humphreys RC, Hennighausen L. Signal transducer and activator of transcription 5a influences mammary epithelial cell survival and tumorigenesis. Cell Growth Differ. 1999;10(10):685–94.PubMed

66.

Ren S, Cai HR, Li M, Furth PA. Loss of Stat5a delays mammary cancer progression in a mouse model. Oncogene. 2002;21(27):4335–9.PubMed

67.

Oakes SR, Robertson FG, Kench JG, Gardiner-Garden M, Wand MP, Green JE, et al. Loss of mammary epithelial prolactin receptor delays tumor formation by reducing cell proliferation in low-grade preinvasive lesions. Oncogene. 2007;26(4):543–53.PubMed

68.

Nevalainen MT, Xie J, Torhorst J, Bubendorf L, Haas P, Kononen J, et al. Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J Clin Oncol. 2004;22(11):2053–60.PubMed

69.

Matulka LA, Wagner K-U. Models of breast cancer. Drug Discov Today 2005;2:1–6.

70.

Utama FE, Lebaron MJ, Neilson LM, Sultan AS, Parlow AF, Wagner KU, et al. Human prolactin receptors are insensitive to mouse prolactin: implications for xenotransplant modeling of human breast cancer in mice. J Endocrinol. 2006;188(3):589–601.PubMed

71.

Watson CJ, Miller WR. Elevated levels of members of the STAT family of transcription factors in breast carcinoma nuclear extracts. Br J Cancer. 1995;71(4):840–4.PubMed

72.

Yamashita H, Nishio M, Ando Y, Zhang Z, Hamaguchi M, Mita K, et al. Stat5 expression predicts response to endocrine therapy and improves survival in estrogen receptor-positive breast cancer. Endocr Relat Cancer. 2006;13(3):885–93.PubMed

73.

Bratthauer GL, Strauss BL, Tavassoli FA. STAT 5a expression in various lesions of the breast. Virchows Arch. 2006;448(2):165–71.PubMed

74.

Strauss BL, Bratthauer GL, Tavassoli FA. STAT 5a expression in the breast is maintained in secretory carcinoma, in contrast to other histologic types. Hum Pathol. 2006;37(5):586–92.PubMed

75.

Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT, Rui H. Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene. 2005;24(5):746–60.PubMed

76.

Gutzman JH, Rugowski DE, Nikolai SE, Schuler LA. Stat5 activation inhibits prolactin-induced AP-1 activity: distinct prolactin-initiated signals in tumorigenesis dependent on cell context. Oncogene. 2007;26(43):6341–8.PubMed

77.

Barash I. Stat5 in the mammary gland: controlling normal development and cancer. J Cell Physiol. 2006;209(2):305–13.PubMed

78.

Nouhi Z, Chughtai N, Hartley S, Cocolakis E, Lebrun JJ, Ali S. Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells. Cancer Res. 2006;66(3):1824–32.PubMed

79.

Maus MV, Reilly SC, Clevenger CV. Prolactin as a chemoattractant for human breast carcinoma. Endocrinology. 1999;140(11):5447–50.PubMed

80.

Manni A, Wright C, Davis G, Glenn J, Joehl R, Feil P. Promotion by prolactin of the growth of human breast neoplasms cultured in vitro in the soft agar clonogenic assay. Cancer Res. 1986;46(4 Pt 1):1669–72.PubMed

81.

Yamashita H, Iwase H. The role of Stat5 in estrogen receptor-positive breast cancer. Breast Cancer 2002;9(4):312–8.PubMed

82.

Yamashita H, Nishio M, Fujii Y, Iwase H. Dominant-negative Stat5 inhibits growth and induces apoptosis in T47D-derived tumors in nude mice. Cancer Sci. 2004;95(8):662–5.PubMed

83.

Boerner JL, Biscardi JS, Silva CM, Parsons SJ. Transactivating agonists of the EGF receptor require Tyr 845 phosphorylation for induction of DNA synthesis. Mol Carcinog. 2005;44(4):262–73.PubMed

84.

Weaver AM, Silva CM. Modulation of signal transducer and activator of transcription 5b activity in breast cancer cells by mutation of tyrosines within the transactivation domain. Mol Endocrinol. 2006;20(10):2392–405.PubMed

85.

Weaver AM, Silva CM. Signal transducer and activator of transcription 5b (STAT5b): a new target of breast tumor kinase/protein tyrosine kinase 6 (Brk/PTK6). Breast Cancer Res. 2007;9(6):R79.PubMed

86.

Boerner JL, Gibson MA, Fox EM, Posner ED, Parsons SJ, Silva CM, et al. Estrogen negatively regulates EGF-mediated STAT5 signaling in HER family receptor overexpressing breast cancer cells. Mol Endocrinol. 2005;19:2660–70.PubMed

87.

Gass S, Harris J, Ormandy C, Brisken C. Using gene expression arrays to elucidate transcriptional profiles underlying prolactin function. J Mammary Gland Biol Neoplasia. 2003;8(3):269–85.PubMed

88.

Clarkson RW, Boland MP, Kritikou EA, Lee JM, Freeman TC, Tiffen PG, et al. The genes induced by signal transducer and activators of transcription (STAT)3 and STAT5 in mammary epithelial cells define the roles of these STATs in mammary development. Mol Endocrinol. 2006;20(3):675–85.PubMed

89.

LeBaron MJ, Xie J, Rui H. Evaluation of genome-wide chromatin library of Stat5 binding sites in human breast cancer. Mol Cancer. 2005;4(1):6.PubMed

90.

Fantl V, Stamp G, Andrews A, Rosewell I, Dickson C. Mice lacking Cyclin D1 are small and show defects in eye and mammary gland development. Genes Dev. 1995;9(19):2364–72.PubMed

91.

Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, et al. Cyclin D1 provides a link between development and oncogenesis in the retina and breast. Cell. 1995;82(4):621–30.PubMed

92.

Brockman JL, Schroeder MD, Schuler LA. PRL activates the Cyclin D1 promoter via the Jak2/Stat pathway. Mol Endocrinol. 2002;16(4):774–84.PubMed

93.

Brockman JL, Schuler LA. Prolactin signals via Stat5 and Oct-1 to the proximal Cyclin D1 promoter. Mol Cell Endocrinol. 2005;239(1–2):45–53.PubMed

94.

Brisken C, Ayyannan A, Nguyen C, Heineman A, Reinhardt F, Tan J, et al. IGF-2 is a mediator of prolactin-induced morphogenesis in the breast. Dev Cell. 2002;3(6):877–87.PubMed

95.

Ruchatz H, Coluccia AM, Stano P, Marchesi E, Gambacorti-Passerini C. Constitutive activation of Jak2 contributes to proliferation and resistance to apoptosis in NPM/ALK-transformed cells. Exp Hematol. 2003;31(4):309–15.PubMed

96.

Slupianek A, Hoser G, Majsterek I, Bronisz A, Malecki M, Blasiak J, et al. Fusion tyrosine kinases induce drug resistance by stimulation of homology-dependent recombination repair, prolongation of G(2)/M phase, and protection from apoptosis. Mol Cell Biol. 2002;22(12):4189–201.PubMed

97.

Baxter EJ, Scott LM, Campbell PJ, East C, Fourouclas N, Swanton S, et al. Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders. Lancet. 2005;365(9464):1054–61.PubMed

98.

James C, Ugo V, Le Couedic JP, Staerk J, Delhommeau F, Lacout C, et al. A unique clonal JAK2 mutation leading to constitutive signalling causes polycythaemia vera. Nature. 2005;434(7037):1144–8.PubMed

99.

Lee JW, Kim YG, Soung YH, Han KJ, Kim SY, Rhim HS, et al. The JAK2 V617F mutation in de novo acute myelogenous leukemias. Oncogene. 2006;25(9):1434–6.PubMed

100.

Arnould C, Philippe C, Bourdon V, Gr goire MJ, Berger R, Jonveaux P. The signal transducer and activator of transcription STAT5b gene is a new partner of retinoic acid receptor alpha in acute promyelocytic-like leukaemia. Hum Mol Genet. 1999;8(9):1741–9.PubMed

101.

Kofoed EM, Hwa V, Little B, Woods KA, Buckway CK, Tsubaki J, et al. Growth hormone insensitivity associated with a STAT5b mutation. N Engl J Med. 2003;349(12):1139–47.PubMed

102.

Hwa V, Little B, Adiyaman P, Kofoed EM, Pratt KL, Ocal G, et al. Severe growth hormone insensitivity resulting from total absence of signal transducer and activator of transcription 5b. J Clin Endocrinol Metab. 2005;90(7):4260–6.PubMed

Titel: Jak2/Stat5 Signaling in Mammogenesis, Breast Cancer Initiation and Progression
verfasst von: Kay-Uwe Wagner
Hallgeir Rui
Publikationsdatum: 01.03.2008
Verlag: Springer US
Erschienen in: Journal of Mammary Gland Biology and Neoplasia / Ausgabe 1/2008
Print ISSN: 1083-3021
Elektronische ISSN: 1573-7039
DOI: https://doi.org/10.1007/s10911-008-9062-z

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Jak2/Stat5 Signaling in Mammogenesis, Breast Cancer Initiation and Progression

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