Stat5 Regulates the Phosphatidylinositol 3-Kinase/Akt1 Pathway during Mammary Gland Development and Tumorigenesis

REFERENCES

• Schmitt-Ney M, Doppler W, Ball RK, Groner B. 1991. Beta-casein gene promoter activity is regulated by the hormone-mediated relief of transcriptional repression and a mammary-gland-specific nuclear factor. Mol. Cell. Biol. 11:3745–3755.
   PubMed Web of Science ®Google Scholar
• Wakao H, Schmitt-Ney M, Groner B. 1992. Mammary gland-specific nuclear factor is present in lactating rodent and bovine mammary tissue and composed of a single polypeptide of 89 kDa. J. Biol. Chem. 267:16365–16370.
   PubMedGoogle Scholar
• Liu X, Robinson GW, Gouilleux F, Groner B, Hennighausen L. 1995. Cloning and expression of Stat5 and an additional homologue (Stat5b) involved in prolactin signal transduction in mouse mammary tissue. Proc. Natl. Acad. Sci. U. S. A. 92:8831–8835. http://dx.doi.org/10.1073/pnas.92.19.8831.
   PubMedGoogle Scholar
• Liu X, Robinson GW, Wagner KU, Garrett L, Wynshaw-Boris A, Hennighausen L. 1997. Stat5a is mandatory for adult mammary gland development and lactogenesis. Genes Dev. 11:179–186. http://dx.doi.org/10.1101/gad.11.2.179.
   PubMed Web of Science ®Google Scholar
• Udy GB, Towers RP, Snell RG, Wilkins RJ, Park SH, Ram PA, Waxman DJ, Davey HW. 1997. Requirement of STAT5b for sexual dimorphism of body growth rates and liver gene expression. Proc. Natl. Acad. Sci. U. S. A. 94:7239–7244. http://dx.doi.org/10.1073/pnas.94.14.7239.
   PubMed Web of Science ®Google Scholar
• Teglund S, McKay C, Schuetz E, van Deursen JM, Stravopodis D, Wang D, Brown M, Bodner S, Grosveld G, Ihle JN. 1998. Stat5a and Stat5b proteins have essential and nonessential, or redundant, roles in cytokine responses. Cell 93:841–850. http://dx.doi.org/10.1016/S0092-8674(00)81444-0.
   PubMed Web of Science ®Google Scholar
• Liu X, Gallego MI, Smith GH, Robinson GW, Hennighausen L. 1998. Functional release of Stat5a-null mammary tissue through the activation of compensating signals including Stat5b. Cell Growth Differ. 9:795–803.
   PubMedGoogle Scholar
• Yamaji D, Na R, Feuermann Y, Pechhold S, Chen W, Robinson GW, Hennighausen L. 2009. Development of mammary luminal progenitor cells is controlled by the transcription factor STAT5A. Genes Dev. 23:2382–2387. http://dx.doi.org/10.1101/gad.1840109.
   PubMedGoogle Scholar
• Wagner KU, Krempler A, Triplett AA, Qi Y, George NM, Zhu J, Rui H. 2004. Impaired alveologenesis and maintenance of secretory mammary epithelial cells in Jak2 conditional knockout mice. Mol. Cell. Biol. 24:5510–5520. http://dx.doi.org/10.1128/MCB.24.12.5510-5520.2004.
   PubMed Web of Science ®Google Scholar
• Cui Y, Riedlinger G, Miyoshi K, Tang W, Li C, Deng CX, Robinson GW, Hennighausen L. 2004. Inactivation of Stat5 in mouse mammary epithelium during pregnancy reveals distinct functions in cell proliferation, survival, and differentiation. Mol. Cell. Biol. 24:8037–8047. http://dx.doi.org/10.1128/MCB.24.18.8037-8047.2004.
   PubMed Web of Science ®Google Scholar
• Li M, Liu X, Robinson G, Bar-Peled U, Wagner KU, Young WS, Hennighausen L, Furth PA. 1997. Mammary-derived signals activate programmed cell death during the first stage of mammary gland involution. Proc. Natl. Acad. Sci. U. S. A. 94:3425–3430. http://dx.doi.org/10.1073/pnas.94.7.3425.
   PubMedGoogle Scholar
• Kritikou EA, Sharkey A, Abell K, Came PJ, Anderson E, Clarkson RW, Watson CJ. 2003. A dual, non-redundant, role for LIF as a regulator of development and STAT3-mediated cell death in mammary gland. Development 130:3459–3468. http://dx.doi.org/10.1242/dev.00578.
   PubMed Web of Science ®Google Scholar
• Tiffen PG, Omidvar N, Marquez-Almuina N, Croston D, Watson CJ, Clarkson RW. 2008. A dual role for oncostatin M signaling in the differentiation and death of mammary epithelial cells in vivo. Mol. Endocrinol. 22:2677–2688. http://dx.doi.org/10.1210/me.2008-0097.
   PubMed Web of Science ®Google Scholar
• Iavnilovitch E, Groner B, Barash I. 2002. Overexpression and forced activation of stat5 in mammary gland of transgenic mice promotes cellular proliferation, enhances differentiation, and delays postlactational apoptosis. Mol. Cancer Res. 1:32–47. http://mcr.aacrjournals.org/content/1/1/32.long.
   PubMed Web of Science ®Google Scholar
• Creamer BA, Sakamoto K, Schmidt JW, Triplett AA, Moriggl R, Wagner KU. 2010. Stat5 promotes survival of mammary epithelial cells through transcriptional activation of a distinct promoter in Akt1. Mol. Cell. Biol. 30:2957–2970. http://dx.doi.org/10.1128/MCB.00851-09.
   PubMedGoogle Scholar
• Vafaizadeh V, Klemmt P, Brendel C, Weber K, Doebele C, Britt K, Grez M, Fehse B, Desrivieres S, Groner B. 2010. Mammary epithelial reconstitution with gene-modified stem cells assigns roles to Stat5 in luminal alveolar cell fate decisions, differentiation, involution, and mammary tumor formation. Stem Cells 28:928–938. http://dx.doi.org/10.1002/stem.407.
   PubMed Web of Science ®Google Scholar
• Caffarel MM, Zaragoza R, Pensa S, Li J, Green AR, Watson CJ. 2012. Constitutive activation of JAK2 in mammary epithelium elevates Stat5 signalling, promotes alveologenesis and resistance to cell death, and contributes to tumourigenesis. Cell Death Differ. 19:511–522. http://dx.doi.org/10.1038/cdd.2011.122.
   PubMedGoogle Scholar
• Schwertfeger KL, Richert MM, Anderson SM. 2001. Mammary gland involution is delayed by activated Akt in transgenic mice. Mol. Endocrinol. 15:867–881. http://press.endocrine.org/doi/full/10.1210/mend.15.6.0663.
   Google Scholar
• Hutchinson J, Jin J, Cardiff RD, Woodgett JR, Muller WJ. 2001. Activation of Akt (protein kinase B) in mammary epithelium provides a critical cell survival signal required for tumor progression. Mol. Cell. Biol. 21:2203–2212. http://dx.doi.org/10.1128/MCB.21.6.2203-2212.2001.
   PubMed Web of Science ®Google Scholar
• Ackler S, Ahmad S, Tobias C, Johnson MD, Glazer RI. 2002. Delayed mammary gland involution in MMTV-AKT1 transgenic mice. Oncogene 21:198–206. http://dx.doi.org/10.1038/sj.onc.1205052.
   PubMedGoogle Scholar
• Abell K, Watson CJ. 2005. The Jak/Stat pathway: a novel way to regulate PI3K activity. Cell Cycle 4:897–900. http://dx.doi.org/10.4161/cc.4.7.1837.
   PubMed Web of Science ®Google Scholar
• Nyga R, Pecquet C, Harir N, Gu H, Dhennin-Duthille I, Regnier A, Gouilleux-Gruart V, Lassoued K, Gouilleux F. 2005. Activated STAT5 proteins induce activation of the PI 3-kinase/Akt and Ras/MAPK pathways via the Gab2 scaffolding adapter. Biochem. J. 390:359–366. http://dx.doi.org/10.1042/BJ20041523.
   PubMed Web of Science ®Google Scholar
• Sakamoto K, Creamer BA, Triplett AA, Wagner KU. 2007. The Janus kinase 2 is required for expression and nuclear accumulation of cyclin D1 in proliferating mammary epithelial cells. Mol. Endocrinol. 21:1877–1892. http://dx.doi.org/10.1210/me.2006-0316.
   PubMedGoogle Scholar
• Creamer BA, Triplett AA, Wagner KU. 2009. Longitudinal analysis of mammogenesis using a novel tetracycline-inducible mouse model and in vivo imaging. Genesis 47:234–245. http://dx.doi.org/10.1002/dvg.20480.
   PubMedGoogle Scholar
• Lin WC, Schmidt JW, Creamer BA, Triplett AA, Wagner KU. 2013. Gain-of-function of Stat5 leads to excessive granulopoiesis and lethal extravasation of granulocytes to the lung. PLoS One 8:e60902. http://dx.doi.org/10.1371/journal.pone.0060902.
   PubMedGoogle Scholar
• Mao C, Tili EG, Dose M, Haks MC, Bear SE, Maroulakou I, Horie K, Gaitanaris GA, Fidanza V, Ludwig T, Wiest DL, Gounari F, Tsichlis PN. 2007. Unequal contribution of Akt isoforms in the double-negative to double-positive thymocyte transition. J. Immunol. 178:5443–5453. http://www.jimmunol.org/content/178/9/5443.long.
   PubMedGoogle Scholar
• Wang H, Karikomi M, Naidu S, Rajmohan R, Caserta E, Chen HZ, Rawahneh M, Moffitt J, Stephens JA, Fernandez SA, Weinstein M, Wang D, Sadee W, La Perle K, Stromberg P, Rosol TJ, Eng C, Ostrowski MC, Leone G. 2010. Allele-specific tumor spectrum in pten knockin mice. Proc. Natl. Acad. Sci. U. S. A. 107:5142–5147. http://dx.doi.org/10.1073/pnas.0912524107.
   PubMedGoogle Scholar
• Perl AK, Wert SE, Nagy A, Lobe CG, Whitsett JA. 2002. Early restriction of peripheral and proximal cell lineages during formation of the lung. Proc. Natl. Acad. Sci. U. S. A. 99:10482–10487. http://dx.doi.org/10.1073/pnas.152238499.
   PubMed Web of Science ®Google Scholar
• Wagner KU, Wall RJ, St-Onge L, Gruss P, Wynshaw-Boris A, Garrett L, Li M, Furth PA, Hennighausen L. 1997. Cre-mediated gene deletion in the mammary gland. Nucleic Acids Res. 25:4323–4330. http://dx.doi.org/10.1093/nar/25.21.4323.
   PubMed Web of Science ®Google Scholar
• Sakamoto K, Schmidt JW, Wagner KU. 2012. Generation of a novel MMTV-tTA transgenic mouse strain for the targeted expression of genes in the embryonic and postnatal mammary gland. PLoS One 7:e43778. http://dx.doi.org/10.1371/journal.pone.0043778.
   PubMed Web of Science ®Google Scholar
• Wagner KU, Young WS, Liu X, Ginns EI, Li M, Furth PA, Hennighausen L. 1997. Oxytocin and milk removal are required for post-partum mammary-gland development. Genes Function 1:233–244. http://dx.doi.org/10.1046/j.1365-4624.1997.00024.x.
   PubMedGoogle Scholar
• LeBaron MJ, Xie J, Rui H. 2005. Evaluation of genome-wide chromatin library of Stat5 binding sites in human breast cancer. Mol. Cancer 4:6–16. http://dx.doi.org/10.1186/1476-4598-4-6.
   PubMedGoogle Scholar
• Abell K, Bilancio A, Clarkson RW, Tiffen PG, Altaparmakov AI, Burdon TG, Asano T, Vanhaesebroeck B, Watson CJ. 2005. Stat3-induced apoptosis requires a molecular switch in PI(3)K subunit composition. Nat. Cell Biol. 7:392–398. http://dx.doi.org/10.1038/ncb1242.
   PubMedGoogle Scholar
• Maroulakou IG, Oemler W, Naber SP, Klebba I, Kuperwasser C, Tsichlis PN. 2008. Distinct roles of the three Akt isoforms in lactogenic differentiation and involution. J. Cell. Physiol. 217:468–477. http://dx.doi.org/10.1002/jcp.21518.
   PubMed Web of Science ®Google Scholar
• Yamaji D, Kang K, Robinson GW, Hennighausen L. 2013. Sequential activation of genetic programs in mouse mammary epithelium during pregnancy depends on STAT5A/B concentration. Nucleic Acids Res. 41:1622–1636. http://dx.doi.org/10.1093/nar/gks1310.
   PubMed Web of Science ®Google Scholar
• Hynes NE, Watson CJ. 2010. Mammary gland growth factors: roles in normal development and in cancer. Cold Spring Harb. Perspect. Biol. 2:a003186. http://dx.doi.org/10.1101/cshperspect.a003186.
   PubMed Web of Science ®Google Scholar
• Gourdou I, Paly J, Hue-Beauvais C, Pessemesse L, Clark J, Djiane J. 2004. Expression by transgenesis of a constitutively active mutant form of the prolactin receptor induces premature abnormal development of the mouse mammary gland and lactation failure. Biol. Reprod. 70:718–728. http://dx.doi.org/10.1095/biolreprod.103.019448.
   PubMedGoogle Scholar
• Weber MS, Boyle PL, Corl BA, Wong EA, Gwazdauskas FC, Akers RM. 1998. Expression of ovine insulin-like growth factor-1 (IGF-1) stimulates alveolar bud development in mammary glands of transgenic mice. Endocrine 8:251–259. http://dx.doi.org/10.1385/ENDO:8:3:251.
   PubMedGoogle Scholar
• Neuenschwander S, Schwartz A, Wood TL, Roberts CTJr, Hennighausen L, LeRoith D. 1996. Involution of the lactating mammary gland is inhibited by the IGF system in a transgenic mouse model. J. Clin. Invest. 97:2225–2232. http://dx.doi.org/10.1172/JCI118663.
   PubMed Web of Science ®Google Scholar
• Sandgren EP, Schroeder JA, Qui TH, Palmiter RD, Brinster RL, Lee DC. 1995. Inhibition of mammary gland involution is associated with transforming growth factor alpha but not c-myc-induced tumorigenesis in transgenic mice. Cancer Res. 55:3915–3927.
   PubMed Web of Science ®Google Scholar
• Dong J, Tong T, Reynado AM, Rosen JM, Huang S, Li Y. 2010. Genetic manipulation of individual somatic mammary cells in vivo reveals a master role of STAT5a in inducing alveolar fate commitment and lactogenesis even in the absence of ovarian hormones. Dev. Biol. 346:196–203. http://dx.doi.org/10.1016/j.ydbio.2010.07.027.
   PubMedGoogle Scholar
• Meyer DS, Brinkhaus H, Muller U, Muller M, Cardiff RD, Bentires-Alj M. 2011. Luminal expression of PIK3CA mutant H1047R in the mammary gland induces heterogeneous tumors. Cancer Res. 71:4344–4351. http://dx.doi.org/10.1158/0008-5472.CAN-10-3827.
   PubMedGoogle Scholar
• Yuan W, Stawiski E, Janakiraman V, Chan E, Durinck S, Edgar KA, Kljavin NM, Rivers CS, Gnad F, Roose-Girma M, Haverty PM, Fedorowicz G, Heldens S, Soriano RH, Zhang Z, Wallin JJ, Johnson L, Merchant M, Modrusan Z, Stern HM, Seshagiri S. 2013. Conditional activation of Pik3ca(H1047R) in a knock-in mouse model promotes mammary tumorigenesis and emergence of mutations. Oncogene 32:318–326. http://dx.doi.org/10.1038/onc.2012.53.
   PubMedGoogle Scholar
• Li G, Robinson GW, Lesche R, Martinez-Diaz H, Jiang Z, Rozengurt N, Wagner KU, Wu DC, Lane TF, Liu X, Hennighausen L, Wu H. 2002. Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland. Development 129:4159–4170. http://dev.biologists.org/content/129/17/4159.long.
   PubMed Web of Science ®Google Scholar
• Chen CC, Boxer RB, Stairs DB, Portocarrero CP, Horton RH, Alvarez JV, Birnbaum MJ, Chodosh LA. 2010. Akt is required for Stat5 activation and mammary differentiation. Breast Cancer Res. 12:R72. http://dx.doi.org/10.1186/bcr2640.
   PubMedGoogle Scholar
• Chen CC, Stairs DB, Boxer RB, Belka GK, Horseman ND, Alvarez JV, Chodosh LA. 2012. Autocrine prolactin induced by the Pten-Akt pathway is required for lactation initiation and provides a direct link between the Akt and Stat5 pathways. Genes Dev. 26:2154–2168. http://dx.doi.org/10.1101/gad.197343.112.
   PubMed Web of Science ®Google Scholar
• Chapman RS, Lourenco PC, Tonner E, Flint DJ, Selbert S, Takeda K, Akira S, Clarke AR, Watson CJ. 1999. Suppression of epithelial apoptosis and delayed mammary gland involution in mice with a conditional knockout of Stat3. Genes Dev. 13:2604–2616. http://dx.doi.org/10.1101/gad.13.19.2604.
   PubMed Web of Science ®Google Scholar
• Humphreys RC, Bierie B, Zhao L, Raz R, Levy D, Hennighausen L. 2002. Deletion of Stat3 blocks mammary gland involution and extends functional competence of the secretory epithelium in the absence of lactogenic stimuli. Endocrinology 143:3641–3650. http://dx.doi.org/10.1210/en.2002-220224.
   PubMed Web of Science ®Google Scholar
• Wagner KU, Schmidt JW. 2011. The two faces of Janus kinases and their respective STATs in mammary gland development and cancer. J. Carcinog. 10:32. http://dx.doi.org/10.4103/1477-3163.90677.
   PubMedGoogle Scholar
• Nevalainen MT, Xie J, Torhorst J, Bubendorf L, Haas P, Kononen J, Sauter G, Rui H. 2004. Signal transducer and activator of transcription-5 activation and breast cancer prognosis. J. Clin. Oncol. 22:2053–2060. http://dx.doi.org/10.1200/JCO.2004.11.046.
   PubMed Web of Science ®Google Scholar
• Cotarla I, Ren S, Zhang Y, Gehan E, Singh B, Furth PA. 2004. Stat5a is tyrosine phosphorylated and nuclear localized in a high proportion of human breast cancers. Int. J. Cancer 108:665–671. http://dx.doi.org/10.1002/ijc.11619.
   PubMed Web of Science ®Google Scholar
• Sakamoto K, Lin WC, Triplett AA, Wagner KU. 2009. Targeting janus kinase 2 in Her2/neu-expressing mammary cancer: implications for cancer prevention and therapy. Cancer Res. 69:6642–6650. http://dx.doi.org/10.1158/0008-5472.CAN-09-0746.
   PubMedGoogle Scholar
• Sakamoto K, Triplett AA, Schuler LA, Wagner KU. 2010. Janus kinase 2 is required for the initiation but not maintenance of prolactin-induced mammary cancer. Oncogene 29:5359–5369. http://dx.doi.org/10.1038/onc.2010.274.
   PubMed Web of Science ®Google Scholar