Stat5 regulates the phosphatidylinositol 3-Kinase/Akt1 pathway during mammary gland development and tumorigenesis

Molecular and Cellular Biology

Volumn 34, Issue 7, 2014, Pages 1363-1377

  Schmidt, Jeffrey W ^a   Wehde, Barbara L ^a   Sakamoto, Kazuhito ^a   Triplett, Aleata A ^a   Anderson, Steven M ^b   Tsichlis, Philip N ^c   Leone, Gustavo ^d   Wagner, Kay Uwe ^a,e  

^a UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

^b UNIVERSITY OF COLORADO SCHOOL OF MEDICINE   (United States)

^c TUFTS MEDICAL CENTER   (United States)

^d OHIO STATE UNIVERSITY   (United States)

^e UNIVERSITY OF NEBRASKA MEDICAL CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA CASEIN; DOXYCYCLINE; JANUS KINASE 1; MESSENGER RNA; PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3 KINASE P110ALPHA; PHOSPHATIDYLINOSITOL 3 KINASE P85ALPHA; PROTEIN KINASE B; STAT3 PROTEIN; STAT5 PROTEIN; STAT5A PROTEIN; STAT5B PROTEIN; UNCLASSIFIED DRUG;

ALLELE; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BIOLUMINESCENCE; BREAST CANCER; BREAST CARCINOGENESIS; BREAST DEVELOPMENT; BREAST EPITHELIUM; BREAST HYPERPLASIA; CELL SURVIVAL; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; COWDEN SYNDROME; FEMALE; IN VIVO STUDY; LACTATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN PHOSPHORYLATION; REAL TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SIGNAL TRANSDUCTION; TUMOR VOLUME; UPREGULATION; WESTERN BLOTTING; WILD TYPE;

ANIMALS; CELL LINE; CLASS I PHOSPHATIDYLINOSITOL 3-KINASES; CLASS IA PHOSPHATIDYLINOSITOL 3-KINASE; FEMALE; GENE KNOCKOUT TECHNIQUES; HAMARTOMA SYNDROME, MULTIPLE; HUMANS; JANUS KINASE 2; MAMMARY GLANDS, ANIMAL; MAMMARY NEOPLASMS, EXPERIMENTAL; MICE; MICE, KNOCKOUT; MICE, MUTANT STRAINS; MICE, TRANSGENIC; PHOSPHATIDYLINOSITOL 3-KINASES; PRECANCEROUS CONDITIONS; PREGNANCY; PROTO-ONCOGENE PROTEINS C-AKT; PTEN PHOSPHOHYDROLASE; RNA, MESSENGER; SIGNAL TRANSDUCTION; STAT5 TRANSCRIPTION FACTOR;

EID: 84895779092     PISSN: 02707306     EISSN: 10985549     Source Type: Journal    
DOI: 10.1128/MCB.01220-13     Document Type: Article

References (53)

1. 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.
2. 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.
3. 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.
4. 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.
5. 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.
6. 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.
7. 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.
8. 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.
9. 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.
10. 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.
11. 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.
12. 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.
13. 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.
14. 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.
15. 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.
16. 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.
17. 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.
18. 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.
19. 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.
20. 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.
21. 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.
22. 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.
23. 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.
24. 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.
25. 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.
26. 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.
27. 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.
28. 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.
29. 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.
30. 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.
31. Wagner KU, Young WS, Liu X, Ginns EI, Li M, Furth PA, Hennighausen L. 1997. Oxytocin and milk removal are required for postpartum mammary-gland development. Genes Function 1:233-244. http://dx.doi.org/10.1046/j.1365-4624.1997.00024.x.
32. 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.
33. 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.
34. 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.
35. 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.
36. 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.
37. 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.
38. 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.
39. Neuenschwander S, Schwartz A, Wood TL, Roberts CT, Jr, 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.
40. 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.
41. 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.
42. 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.
43. 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.
44. 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.
45. 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.
46. 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.
47. 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.
48. 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.
49. 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.
50. 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.
51. 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.
52. 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.
53. 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.