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Modeling Prolactin Actions in Breast Cancer In Vivo: Insights from the NRL-PRL Mouse

  • Kathleen A. O’LearyEmail author
  • Michael P. Shea
  • Linda A. Schuler
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 846)

Abstract

Elevated exposure to prolactin (PRL) is epidemiologically associated with an increased risk of aggressive ER+ breast cancer. To understand the underlying mechanisms and crosstalk with other oncogenic factors, we developed the NRL-PRL mouse. In this model, mammary expression of a rat prolactin transgene raises local exposure to PRL without altering estrous cycling. Nulliparous females develop metastatic, histotypically diverse mammary carcinomas independent from ovarian steroids, and most are ER+. These characteristics resemble the human clinical disease, facilitating study of tumorigenesis, and identification of novel preventive and therapeutic approaches.

Keywords

Breast Cancer Mammary Gland Ovarian Steroid Nulliparous Female erbB Family Member 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgements

The authors would like to thank Gail Loughridge for her assistance with the illustration, and are grateful to the National Cancer Institute of the National Institutes of Health, the Congressionally Directed Medical Research Program, the Department of Comparative Biosciences at the School of Veterinary Medicine, and Carbone Comprehensive Cancer Center, University of Wisconsin, Madison, for support of these studies.

References

  1. 1.
    Oakes SR, Rogers RL, Naylor MJ, Ormandy CJ (2008) Prolactin regulation of mammary gland development. J Mammary Gland Biol Neoplasia 13:13–28PubMedGoogle Scholar
  2. 2.
    Tworoger SS, Hankinson SE (2008) Prolactin and breast cancer etiology: an epidemiologic perspective. J Mammary Gland Biol Neoplasia 13:41–53PubMedGoogle Scholar
  3. 3.
    Fernandez I, Touraine P, Goffin V (2010) Prolactin and human tumourogenesis. J Neuroendocrinol 22:771–777PubMedGoogle Scholar
  4. 4.
    Jacobson EM, Hugo ER, Borcherding DC, Ben-Jonathan N (2011) Prolactin in breast and prostate cancer: molecular and genetic perspectives. Discov Med 11:315–324PubMedGoogle Scholar
  5. 5.
    Tworoger SS, Eliassen AH, Zhang X, Qian J, Sluss PM et al (2013) A 20-year prospective study of plasma prolactin as a risk marker of breast cancer development. Cancer Res 73:4810–4819PubMedCentralPubMedGoogle Scholar
  6. 6.
    Courtillot C, Chakhtoura Z, Bogorad R, Genestie C, Bernichtein S et al (2010) Characterization of two constitutively active prolactin receptor variants in a cohort of 95 women with multiple breast fibroadenomas. J Clin Endocrinol Metab 95:271–279PubMedGoogle Scholar
  7. 7.
    Bogorad RL, Courtillot C, Mestayer C, Bernichtein S, Harutyunyan L et al (2008) Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. Proc Natl Acad Sci USA 105:14533–14538PubMedCentralPubMedGoogle Scholar
  8. 8.
    Mong FY, Kuo YL, Liu CW, Liu WS, Chang LC (2011) Association of gene polymorphisms in prolactin and its receptor with breast cancer risk in Taiwanese women. Mol Biol Rep 38:4629–4636PubMedGoogle Scholar
  9. 9.
    Swaminathan G, Varghese B, Fuchs SY (2008) Regulation of prolactin receptor levels and activity in breast cancer. J Mammary Gland Biol Neoplasia 13:81–91PubMedCentralPubMedGoogle Scholar
  10. 10.
    Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F et al (1998) Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissues. J Clin Endocrinol Metab 83:667–674PubMedGoogle Scholar
  11. 11.
    Wagner KU, Rui H (2008) Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression. J Mammary Gland Biol Neoplasia 13:93–103PubMedGoogle Scholar
  12. 12.
    Peck AR, Witkiewicz AK, Liu C, Klimowicz AC, Stringer GA et al (2012) Low levels of Stat5a protein in breast cancer are associated with tumor progression and unfavorable clinical outcomes. Breast Cancer Res 14:R130PubMedCentralPubMedGoogle Scholar
  13. 13.
    Bole-Feysot C, Goffin V, Edery M, Binart N, Kelly PA (1998) Prolactin (PRL) and its receptor: actions, signal transduction pathways and phenotypes observed in PRL receptor knockout mice. Endocr Rev 19:225–268PubMedGoogle Scholar
  14. 14.
    Vonderhaar BK (1999) Prolactin involvement in breast cancer. Endocr Relat Cancer 6:389–404PubMedGoogle Scholar
  15. 15.
    Clevenger CV, Furth PA, Hankinson SE, Schuler LA (2003) Role of prolactin in mammary carcinoma. Endocr Rev 24:1–27PubMedCentralPubMedGoogle Scholar
  16. 16.
    Howell SJ, Anderson E, Hunter T, Farnie G, Clarke RB (2008) Prolactin receptor antagonism reduces the clonogenic capacity of breast cancer cells and potentiates doxorubicin and paclitaxel cytotoxicity. Breast Cancer Res 10:R68PubMedCentralPubMedGoogle Scholar
  17. 17.
    LaPensee EW, Schwemberger SJ, LaPensee CR, Bahassi EM, Afton S et al (2009) Prolactin confers resistance against cisplatin in breast cancer cells by activating glutathione-S-transferase. Carcinogenesis 30:1298–1304PubMedCentralPubMedGoogle Scholar
  18. 18.
    Sultan AS, Xie J, LeBaron MJ, Ealley EL, Nevalainen MT et al (2005) Stat5 promotes homotypic adhesion and inhibits invasive characteristics of human breast cancer cells. Oncogene 24:746–760PubMedGoogle Scholar
  19. 19.
    Nouhi Z, Chughtai N, Hartley S, Cocolakis E, Lebrun JJ et al (2006) Defining the role of prolactin as an invasion suppressor hormone in breast cancer cells. Cancer Res 66:1824–1832PubMedGoogle Scholar
  20. 20.
    Gutzman JH, Rugowski DE, Nikolai SE, Schuler LA (2007) Stat5 activation inhibits prolactin-induced AP-1 activity: distinct prolactin initiated signals in tumorigenesis dependent on cell context. Oncogene 26:6341–6348PubMedCentralPubMedGoogle Scholar
  21. 21.
    Barcus CE, Keely PJ, Eliceiri KW, Schuler LA (2013) Stiff collagen matrices increase tumorigenic prolactin signaling in breast cancer cells. J Biol Chem 288:12722–12732PubMedCentralPubMedGoogle Scholar
  22. 22.
    Early Breast Cancer Trialists’ Collaborative G (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials Lancet 365:1687–1717Google Scholar
  23. 23.
    Ben Jonathan N, LaPensee CR, LaPensee EW (2008) What can we learn from rodents about prolactin in humans? Endocr Rev 29:1–41PubMedCentralPubMedGoogle Scholar
  24. 24.
    Ginsburg E, Vonderhaar BK (1995) Prolactin synthesis and secretion by human breast cancer cells. Cancer Res 55:2591–2595PubMedGoogle Scholar
  25. 25.
    Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW (1996) Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 17:639–669PubMedGoogle Scholar
  26. 26.
    Shaw-Bruha CM, Pirrucello SJ, Shull JD (1997) Expression of the prolactin gene in normal and neoplastic human breast tissues and human breast cell lines: promoter usage and alternative mRNA splicing. Breast Cancer Res Treat 44:243–253PubMedGoogle Scholar
  27. 27.
    Clevenger CV, Plank TL (1997) Prolactin as an autocrine/ paracrine factor in breast cancer. J Mammary Gland Biol Neoplasia 2:59–68PubMedGoogle Scholar
  28. 28.
    Bhatavdekar JM, Patel DD, Shah NG, Vora HH, Suthar TP et al (2000) Prolactin as a local growth promoter in patients with breast cancer: GCRI experience. Eur J Surg Oncol 26:540–547PubMedGoogle Scholar
  29. 29.
    McHale K, Tomaszewski JE, Puthiyaveettil R, Livolsi VA, Clevenger CV (2008) Altered expression of prolactin receptor-associated signaling proteins in human breast carcinoma. Mod Pathol 21:565–571PubMedGoogle Scholar
  30. 30.
    Baudhuin A, Manfroid I, Van De Weerdt C, Martial JA, Muller M (2002) Transcription of the human prolactin gene in mammary cells. Ann N Y Acad Sci 973:454–458PubMedGoogle Scholar
  31. 31.
    Clevenger CV, Zheng J, Jablonski EM, Galbaugh TL, Fang F (2008) From bench to bedside: future potential for the translation of prolactin inhibitors as breast cancer therapeutics. J Mammary Gland Biol Neoplasia 13:147–156PubMedGoogle Scholar
  32. 32.
    Kurtz A, Bristol LA, Toth BE, Lazar-Wesley E, Takacs L et al (1993) Mammary epithelial cells of lactating rats express prolactin messenger ribonucleic acid. Biol Reprod 48:1095–1103PubMedGoogle Scholar
  33. 33.
    Merson J, Sall W, Mitchner N, Ben-Jonathan N (1995) Prolactin is a local growth factor in rat mammary tumors. Endocrinology 136:3619–3623Google Scholar
  34. 34.
    Naylor MJ, Lockefeer JA, Horseman ND, Ormandy CJ (2003) Prolactin regulates mammary epithelial cell proliferation via autocrine/paracrine mechanism. Endocrine 20:111–114PubMedGoogle Scholar
  35. 35.
    Chen CC, Stairs DB, Boxer RB, Belka GK, Horseman ND et al (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 26:2154–2168PubMedCentralPubMedGoogle Scholar
  36. 36.
    Oliver CH, Watson CJ (2013) Making milk: a new link between STAT5 and Akt1. JAKSTAT 2:e23228PubMedCentralPubMedGoogle Scholar
  37. 37.
    Gutzman JH, Miller KK, Schuler LA (2004) Endogenous hPRL and not exogenous hPRL induces ERα and PRLR expression and increases estrogen responsiveness in breast cancer cells. J Steroid Biochem Mol Biol 88:69–77PubMedGoogle Scholar
  38. 38.
    Soares MJ, Konno T, Alam SM (2007) The prolactin family: effectors of pregnancy-dependent adaptations. Trends Endocrinol Metab 18:114–121PubMedGoogle Scholar
  39. 39.
    Utama FE, Tran TH, Ryder A, LeBaron MJ, Parlow AF et al (2009) Insensitivity of human prolactin receptors to non-human prolactins: relevance for experimental modeling of prolactin receptor-expressing human cells. Endocrinology 150:1782–1790PubMedCentralPubMedGoogle Scholar
  40. 40.
    Welsch CW, Nagasawa H (1977) Prolactin and murine mammary tumorigenesis: a review. Cancer Res 37:951–963PubMedGoogle Scholar
  41. 41.
    Huseby RA, Soares MJ, Talamantes F (1985) Ectopic pituitary grafts in mice: hormone levels, effects on fertility, and the development of adenomyosis uteri, prolactinomas, and mammary carcinomas4. Endocrinology 116:1440–1448PubMedGoogle Scholar
  42. 42.
    Medina D, Kittrell F (2000) Hormonal stimulation of the mouse mammary gland. In: Ip C, Asch BB (eds) Methods in mammary gland biology and breast cancer research. Kluwer Academic, New York, pp 101–107Google Scholar
  43. 43.
    Stocco C, Telleria C, Gibori G (2007) The molecular control of corpus luteum formation, function, and regression. Endocr Rev 28:117–149PubMedGoogle Scholar
  44. 44.
    Anderson SM, Rudolph MC, McManaman JL, Neville MC (2007) Key stages in mammary gland development. Secretory activation in the mammary gland: it’s not just about milk protein synthesis! Breast Cancer Res 9:204PubMedCentralPubMedGoogle Scholar
  45. 45.
    Lee HJ, Ormandy CJ (2012) Interplay between progesterone and prolactin in mammary development and implications for breast cancer. Mol Cell Endocrinol 357:101–107PubMedGoogle Scholar
  46. 46.
    Arendt LM, Schuler LA (2008) Transgenic models to study actions of prolactin in mammary neoplasia. J Mammary Gland Biol Neoplasia 13:29–40PubMedGoogle Scholar
  47. 47.
    Wennbo H, Gebre-Medhin M, Gritli-Linde A, Ohlsson C, Isaksson OGP et al (1997) Activation of the prolactin receptor but not the growth hormone receptor is important for induction of mammary tumors in transgenic mice. J Clin Invest 100:2744–2751PubMedCentralPubMedGoogle Scholar
  48. 48.
    Manhes C, Kayser C, Bertheau P, Kelder B, Kopchick JJ et al (2006) Local over-expression of prolactin in differentiating mouse mammary gland induces functional defects and benign lesions, but no carcinoma. J Endocrinol 190:271–285PubMedGoogle Scholar
  49. 49.
    Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP et al (2003) Prolactin induces ERα-positive and ERα-negative mammary cancer in transgenic mice. Oncogene 22:4664–4674PubMedCentralPubMedGoogle Scholar
  50. 50.
    Koromilas AE, Sexl V (2013) The tumor suppressor function of STAT1 in breast cancer. JAKSTAT 2:e23353PubMedCentralPubMedGoogle Scholar
  51. 51.
    Chan SR, Rickert CG, Vermi W, Sheehan KC, Arthur C et al (2014) Dysregulated STAT1-SOCS1 control of JAK2 promotes mammary luminal progenitor cell survival and drives ERα tumorigenesis. Cell Death Differ. 21:234–246PubMedCentralPubMedGoogle Scholar
  52. 52.
    Linossi EM, Babon JJ, Hilton DJ, Nicholson SE (2013) Suppression of cytokine signaling: the SOCS perspective. Cytokine Growth Factor Rev 24:241–248PubMedGoogle Scholar
  53. 53.
    Inagaki-Ohara K, Kondo T, Ito M, Yoshimura A (2013) SOCS, inflammation, and cancer. JAKSTAT 2:e24053PubMedCentralPubMedGoogle Scholar
  54. 54.
    Rose-Hellekant TA, Schroeder MD, Brockman JL, Zhdankin O, Bolstad R et al (2007) Estrogen receptor positive mammary tumorigenesis in TGFα transgenic mice progresses with progesterone receptor loss. Oncogene 26:5238–5246PubMedCentralPubMedGoogle Scholar
  55. 55.
    Stoesz SP, Gould MN (1995) Overexpression of neu-related lipocalin (NRL) in neu-initiated but not ras or chemically initiated rat mammary carcinomas. Oncogene 11:2233–2241PubMedGoogle Scholar
  56. 56.
    Arendt LM, Evans LC, Rugowski DE, Garcia-Barchino MJ, Rui H et al (2009) Ovarian hormones are not required for PRL-induced mammary tumorigenesis, but estrogen enhances neoplastic processes. J Endocrinol 203:99–110PubMedCentralPubMedGoogle Scholar
  57. 57.
    Arendt LM, Rugowski DE, Grafwallner-Huseth TL, Garcia-Barchino MJ, Rui H et al (2011) Prolactin-induced mouse mammary carcinomas model estrogen resistant luminal breast cancer. Breast Cancer Res 13:R11–25PubMedCentralPubMedGoogle Scholar
  58. 58.
    Sakamoto K, Triplett AA, Schuler LA, Wagner KU (2010) Jak2 is required for the initiation but not maintenance of prolactin-induced mammary cancer. Oncogene 29:5359–5369PubMedCentralPubMedGoogle Scholar
  59. 59.
    Hennighausen L, Robinson GW (2001) Signaling pathways in mammary gland development. Dev Cell 1:467–475PubMedGoogle Scholar
  60. 60.
    Acosta JJ, Munoz RM, Gonzalez L, Subtil-Rodriguez A, Dominguez-Caceres MA et al (2003) Src mediates prolactin-dependent proliferation of T47D and MCF7 cells via the activation of focal adhesion kinase/Erk1/2 and phosphatidylinositol 3-kinase pathways. Mol Endocrinol 17:2268–2282PubMedGoogle Scholar
  61. 61.
    Piazza TM, Lu JC, Carver KC, Schuler LA (2009) Src family kinases accelerate prolactin receptor internalization, modulating trafficking and signaling in breast cancer cells. Mol Endocrinol 23:202–212PubMedCentralPubMedGoogle Scholar
  62. 62.
    Musgrove EA, Caldon CE, Barraclough J, Stone A, Sutherland RL (2011) Cyclin D as a therapeutic target in cancer. Nat Rev Cancer 11:558–572PubMedGoogle Scholar
  63. 63.
    Brisken C, Ayyannan A, Nguyen C, Heineman A, Reinhardt F et al (2002) IGF-2 is a mediator of prolactin-induced morphogenesis in the breast. Dev Cell 3:877–887PubMedGoogle Scholar
  64. 64.
    Asher JM, O’Leary KA, Rugowski DE, Arendt LM, Schuler LA (2012) Prolactin promotes mammary pathogenesis independently from cyclin D1. Am J Pathol 181:294–302PubMedCentralPubMedGoogle Scholar
  65. 65.
    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 21:1877–1892PubMedGoogle Scholar
  66. 66.
    Russell A, Thompson MA, Hendley J, Trute L, Armes J et al (1999) Cyclin D1 and D3 associate with the SCF complex and are coordinately elevated in breast cancer. Oncogene 18:1983–1991PubMedGoogle Scholar
  67. 67.
    Wong SCC, Chan JKC, Lee KC, Hsiao WLW (2001) Differential expression of p16/p21/p27 and cyclin D1/D3, and their relationships to cell proliferation, apoptosis, and tumour progression in invasive ductal carcinoma of the breast. J Pathol 194:35–42PubMedGoogle Scholar
  68. 68.
    Zhang Q, Sakamoto K, Liu C, Triplett AA, Lin WC et al (2011) Cyclin D3 compensates for the loss of Cyclin D1 during ErbB2-induced mammary tumor initiation and progression. Cancer Res 71:7513–7524PubMedCentralPubMedGoogle Scholar
  69. 69.
    Schroeder MD, Symowicz J, Schuler LA (2002) Prolactin modulates cell cycle regulators in mammary tumor epithelial cells. Mol Endocrinol 16:45–57PubMedGoogle Scholar
  70. 70.
    Joshi PA, Jackson HW, Beristain AG, Di Grappa MA, Mote P et al (2010) Progesterone induces adult mammary stem cell expansion. Nature 465:803–807PubMedGoogle Scholar
  71. 71.
    Asselin-Labat ML, Vaillant F, Sheridan JM, Pal B, Wu D et al (2010) Control of mammary stem cell function by steroid hormone signalling. Nature 465:798–802PubMedGoogle Scholar
  72. 72.
    O’Leary KA, Rugowski DE, Sullivan R, Schuler LA (2013) Prolactin cooperates with loss of p53 to promote claudin low mammary carcinomas. Oncogene 33(23):3075–3082PubMedGoogle Scholar
  73. 73.
    Fu N, Lindeman GJ, Visvader JE (2014) The mammary stem cell hierarchy. Curr Top Dev Biol 107:133–160PubMedGoogle Scholar
  74. 74.
    Kalyuga M, Gallego-Ortega D, Lee HJ, Roden DL, Cowley MJ et al (2012) ELF5 suppresses estrogen sensitivity and underpins the acquisition of antiestrogen resistance in luminal breast cancer. PLoS Biol 10:e1001461PubMedCentralPubMedGoogle Scholar
  75. 75.
    Chakrabarti R, Hwang J, Andres Blanco M, Wei Y, Lukacisin M et al (2012) Elf5 inhibits the epithelial-mesenchymal transition in mammary gland development and breast cancer metastasis by transcriptionally repressing Snail2. Nat Cell Biol 14:1212–1222PubMedCentralPubMedGoogle Scholar
  76. 76.
    Arendt LM, Grafwallner-Huseth TL, Schuler LA (2009) Prolactin-growth factor crosstalk reduces mammary estrogen responsiveness despite elevated ERα expression. Am J Pathol 174:1065–1074PubMedCentralPubMedGoogle Scholar
  77. 77.
    Oh DS, Troester MA, Usary J, Hu Z, He X et al (2006) Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol 24:1656–1664PubMedGoogle Scholar
  78. 78.
    Massarweh S, Osborne CK, Creighton CJ, Qin L, Tsimelzon A et al (2008) Tamoxifen resistance in breast tumors is driven by growth factor receptor signaling with repression of classic estrogen receptor genomic function. Cancer Res 68:826–833PubMedGoogle Scholar
  79. 79.
    Creighton CJ (2012) The molecular profile of luminal B breast cancer. Biologics 6:289–297PubMedCentralPubMedGoogle Scholar
  80. 80.
    Mohibi S, Mirza S, Band H, Band V (2011) Mouse models of estrogen receptor-positive breast cancer. J Carcinog 10:35PubMedCentralPubMedGoogle Scholar
  81. 81.
    Kirma NB, Tekmal RR (2012) Transgenic mouse models of hormonal mammary carcinogenesis: advantages and limitations. J Steroid Biochem Mol Biol 131:76–82PubMedGoogle Scholar
  82. 82.
    Dabydeen SA, Furth PA (2014) Genetically engineered ERα positive breast cancer mouse models. Endocr Relat Cancer. 21:R195–R208PubMedCentralPubMedGoogle Scholar
  83. 83.
    Peck AR, Witkiewicz AK, Liu C, Stringer GA, Klimowicz AC et al (2011) Loss of nuclear localized and tyrosine phosphorylated Stat5 in breast cancer predicts poor clinical outcome and increased risk of antiestrogen therapy failure. J Clin Oncol 29:2448–2458PubMedCentralPubMedGoogle Scholar
  84. 84.
    Gutzman JH, Rugowski DE, Schroeder MD, Watters JJ, Schuler LA (2004) Multiple kinase cascades mediate prolactin signals to activating protein-1 in breast cancer cells. Mol Endocrinol 18:3064–3075PubMedCentralPubMedGoogle Scholar
  85. 85.
    Network CGA (2012) Comprehensive molecular portraits of human breast tumours. Nature 490:61–70Google Scholar
  86. 86.
    Ursini-Siegel J, Schade B, Cardiff RD, Muller WJ (2007) Insights from transgenic mouse models of ERBB2-induced breast cancer. Nat Rev Cancer 7:389–397PubMedGoogle Scholar
  87. 87.
    Herschkowitz JI, Zhao W, Zhang M, Usary J, Murrow G et al (2012) Comparative oncogenomics identifies breast tumors enriched in functional tumor-initiating cells. Proc Natl Acad Sci U S A 109:2778–2783PubMedCentralPubMedGoogle Scholar
  88. 88.
    Chan SR, Vermi W, Luo J, Lucini L, Rickert C et al (2012) STAT1-deficient mice spontaneously develop estrogen receptor alpha-positive luminal mammary carcinomas. Breast Cancer Res 14:R16PubMedCentralPubMedGoogle Scholar
  89. 89.
    Gutzman JH, Nikolai SE, Rugowski DE, Watters JJ, Schuler LA (2005) Prolactin and estrogen enhance the activity of Activating Protein-1 in breast cancer cells: role of ERK1/2-mediated signals to c-fos. Mol Endocrinol 19:1765–1778PubMedCentralPubMedGoogle Scholar
  90. 90.
    Chen Y, Huang K, Chen KE, Walker AM (2010) Prolactin and estradiol utilize distinct mechanisms to increase serine-118 phosphorylation and decrease levels of estrogen receptor alpha in T47D breast cancer cells. Breast Cancer Res Treat 120:369–377PubMedGoogle Scholar
  91. 91.
    Rasmussen LM, Frederiksen KS, Din N, Galsgaard E, Christensen L et al (2010) Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells. Endocr Relat Cancer 17:809–822PubMedGoogle Scholar
  92. 92.
    Sato T, Tran TH, Peck AR, Liu C, Ertel A et al (2013) Global profiling of prolactin-modulated transcripts in breast cancer in vivo. Mol Cancer 12:59PubMedCentralPubMedGoogle Scholar
  93. 93.
    Fiorillo AA, Medler TR, Feeney YB, Wetz SM, Tommerdahl KL et al (2013) The prolactin receptor transactivation domain is associated with steroid hormone receptor expression and malignant progression of breast cancer. Am J Pathol 182:217–233PubMedGoogle Scholar
  94. 94.
    Dong J, Tsai-Morris CH, Dufau ML (2006) A novel estradiol/estrogen receptor alpha-dependent transcriptional mechanism controls expression of the human prolactin receptor. J Biol Chem 281:18825–18836PubMedGoogle Scholar
  95. 95.
    Silva CM, Shupnik MA (2007) Integration of steroid and growth factor pathways in breast cancer: focus on signal transducers and activators of transcription and their potential role in resistance. Mol Endocrinol 21:1499–1512PubMedGoogle Scholar
  96. 96.
    Bjornstrom L, Sjoberg M (2002) Signal transducers and activators of transcription as downstream targets of nongenomic estrogen receptor actions. Mol Endocrinol 16:2202–2214PubMedGoogle Scholar
  97. 97.
    Faulds MH, Pettersson K, Gustafsson JA, Haldosen LA (2001) Cross-talk between ERs and signal transducer and activator of transcription 5 is estrogen dependent and involves two functionally separate mechanisms. Mol Endocrinol 15:1929–1940PubMedGoogle Scholar
  98. 98.
    Furth PA, Nakles RE, Millman S, Diaz-Cruz ES, Cabrera MC (2011) Signal transducer and activator of transcription 5 as a key signaling pathway in normal mammary gland developmental biology and breast cancer. Breast Cancer Res 13:220PubMedCentralPubMedGoogle Scholar
  99. 99.
    de Leeuw R, Neefjes J, Michalides R (2011) A role for estrogen receptor phosphorylation in the resistance to tamoxifen. Int J Breast Cancer 2011:232435PubMedCentralPubMedGoogle Scholar
  100. 100.
    O’Leary KA, Jallow F, Rugowski DE, Sullivan R, Sinkevicius KW et al (2013) Prolactin activates ERα in the absence of ligand in female mammary development and carcinogenesis in vivo. Endocrinology 154:4483–4492PubMedCentralPubMedGoogle Scholar
  101. 101.
    Arendt LM, Schuler LA (2008) Prolactin drives ERα-dependent ductal expansion and synergizes with TGFα to induce mammary tumors in males. Am J Pathol 172:194–202PubMedCentralPubMedGoogle Scholar
  102. 102.
    Gonzalez L, Zambrano A, Lazaro-Trueba I, Lopez E, Gonzalez JJ et al (2009) Activation of the unliganded estrogen receptor by prolactin in breast cancer cells. Oncogene 28:1298–1308PubMedGoogle Scholar
  103. 103.
    Sinkevicius KW, Burdette JE, Woloszyn K, Hewitt SC, Hamilton K et al (2008) An estrogen receptor-alpha knock-in mutation provides evidence of ligand-independent signaling and allows modulation of ligand-induced pathways in vivo. Endocrinology 149:2970–2979PubMedCentralPubMedGoogle Scholar
  104. 104.
    Carver KC, Arendt LM, Schuler LA (2009) Complex prolactin crosstalk in breast cancer: new therapeutic implications. Mol Cell Endocrinol 307:1–7PubMedCentralPubMedGoogle Scholar
  105. 105.
    Yarden Y (2001) The EGFR family and its ligands in human cancer: signalling mechanisms and therapeutic opportunities. Eur J Cancer Part A 37:S3–S8Google Scholar
  106. 106.
    Holbro T, Civenni G, Hynes NE (2003) The ErbB receptors and their role in cancer progression. Exp Cell Res 284:99–110PubMedGoogle Scholar
  107. 107.
    Booth BW, Smith GH (2007) Roles of transforming growth factor-alpha in mammary development and disease. Growth Factors 25:227–235PubMedGoogle Scholar
  108. 108.
    Arendt LM, Rose-Hellekant TA, Sandgren EP, Schuler LA (2006) Prolactin potentiates TGFα induction of mammary neoplasia in transgenic mice. Am J Pathol 168:1365–1374PubMedCentralPubMedGoogle Scholar
  109. 109.
    Arendt LM, Rudnick JA, Keller PJ, Kuperwasser C (2010) Stroma in breast development and disease. Semin Cell Dev Biol 21:11–18PubMedCentralPubMedGoogle Scholar
  110. 110.
    Hanahan D, Coussens LM (2012) Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell 21:309–322PubMedGoogle Scholar
  111. 111.
    Joyce JA, Pollard JW (2009) Microenvironmental regulation of metastasis. Nat Rev Cancer 9:239–252PubMedCentralPubMedGoogle Scholar
  112. 112.
    Ali S, Coombes RC (2002) Endocrine-responsive breast cancer and strategies for combating resistance. Nat Rev Cancer 2:101–112PubMedGoogle Scholar
  113. 113.
    Musgrove EA, Sutherland RL (2009) Biological determinants of endocrine resistance in breast cancer. Nat Rev Cancer 9:631–643PubMedGoogle Scholar
  114. 114.
    Osborne CK, Schiff R (2011) Mechanisms of endocrine resistance in breast cancer. Annu Rev Med 62:233–247PubMedCentralPubMedGoogle Scholar
  115. 115.
    Roop RP, Ma CX (2012) Endocrine resistance in breast cancer: molecular pathways and rational development of targeted therapies. Future Oncol 8:273–292PubMedGoogle Scholar
  116. 116.
    Nahleh ZA (2006) Hormonal therapy for male breast cancer: a different approach for a different disease. Cancer Treat Rev 32:101–105PubMedGoogle Scholar
  117. 117.
    White J, Kearins O, Dodwell D, Horgan K, Hanby AM et al (2011) Male breast carcinoma: increased awareness needed. Breast Cancer Res 13:219PubMedCentralPubMedGoogle Scholar
  118. 118.
  119. 119.
    Olsson H, Ranstam J (1988) Head trauma and exposure to prolactin-elevating drugs as risk factors for male breast cancer. J Natl Cancer Inst 80:679–683PubMedGoogle Scholar
  120. 120.
    Olsson H, Alm P, Aspegren K, Gullberg B, Jonsson PE et al (1990) Increased plasma prolactin levels in a group of men with breast cancer–a preliminary study. Anticancer Res 10:59–62PubMedGoogle Scholar
  121. 121.
    Krause W (2004) Male breast cancer–an andrological disease: risk factors and diagnosis. Andrologia 36:346–354PubMedGoogle Scholar
  122. 122.
    Fentiman IS, Fourquet A, Hortobagyi GN (2006) Male breast cancer. Lancet 367:595–604PubMedGoogle Scholar
  123. 123.
    Milde-Langosch K (2005) The Fos family of transcription factors and their role in tumourigenesis. Eur J Cancer 41:2449–2461PubMedGoogle Scholar
  124. 124.
    Zhou Y, Yau C, Gray JW, Chew K, Dairkee SH et al (2007) Enhanced NF kappa B and AP-1 transcriptional activity associated with antiestrogen resistant breast cancer. BMC Cancer 7:59PubMedCentralPubMedGoogle Scholar
  125. 125.
    Conklin MW, Eickhoff JC, Riching KM, Pehlke CA, Eliceiri KW et al (2011) Aligned collagen is a prognostic signature for survival in human breast carcinoma. Am J Pathol 178:1221–1232PubMedCentralPubMedGoogle Scholar
  126. 126.
    Butcher DT, Alliston T, Weaver VM (2009) A tense situation: forcing tumour progression. Nat Rev Cancer 9:108–122PubMedCentralPubMedGoogle Scholar
  127. 127.
    Keely PJ (2011) Mechanisms by which the extracellular matrix and integrin signaling act to regulate the switch between tumor suppression and tumor promotion. J Mammary Gland Biol Neoplasia 16:205–219PubMedGoogle Scholar
  128. 128.
    Martin LJ, Boyd NF (2008) Mammographic density. Potential mechanisms of breast cancer risk associated with mammographic density: hypotheses based on epidemiological evidence. Breast Cancer Res 10:201PubMedCentralPubMedGoogle Scholar
  129. 129.
    Martin LJ, Minkin S, Boyd NF (2009) Hormone therapy, mammographic density, and breast cancer risk. Maturitas 64:20–26PubMedGoogle Scholar
  130. 130.
    Rutter CM, Mandelson MT, Laya MB, Seger DJ, Taplin S (2001) Changes in breast density associated with initiation, discontinuation, and continuing use of hormone replacement therapy. JAMA 285:171–176PubMedGoogle Scholar
  131. 131.
    McCormack VA, dos Santos Silva I (2006) Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15:1159–1169PubMedGoogle Scholar
  132. 132.
    Vachon CM, van Gils CH, Sellers TA, Ghosh K, Pruthi S et al (2007) Mammographic density, breast cancer risk and risk prediction. Breast Cancer Res 9:217PubMedCentralPubMedGoogle Scholar
  133. 133.
    Tamimi SO, Ahmed A (1987) Stromal changes in invasive breast carcinoma: an ultrastructural study. J Pathol 153:163–170PubMedGoogle Scholar
  134. 134.
    Provenzano PP, Inman DR, Eliceiri KW, Knittel JG, Yan L et al (2008) Collagen density promotes mammary tumor initiation and progression. BMC Med 6:11PubMedCentralPubMedGoogle Scholar
  135. 135.
    Levental KR, Yu H, Kass L, Lakins JN, Egeblad M et al (2009) Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139:891–906PubMedCentralPubMedGoogle Scholar
  136. 136.
    Gass S, Harris J, Ormandy C, Brisken C (2003) Using gene expression arrays to elucidate transcriptional profiles underlying prolactin function. J Mammary Gland Biol Neoplasia 8:269–285PubMedGoogle Scholar
  137. 137.
    Soikkeli J, Podlasz P, Yin M, Nummela P, Jahkola T et al (2010) Metastatic outgrowth encompasses COL-I, FN1, and POSTN up-regulation and assembly to fibrillar networks regulating cell adhesion, migration, and growth. Am J Pathol 177:387–403PubMedCentralPubMedGoogle Scholar
  138. 138.
    Orend G, Chiquet-Ehrismann R (2006) Tenascin-C induced signaling in cancer. Cancer Lett 244:143–163PubMedGoogle Scholar
  139. 139.
    Liu X, Wu H, Byrne M, Jeffrey J, Krane S et al (1995) A targeted mutation at the known collagenase cleavage site in mouse type I collagen impairs tissue remodeling. J Cell Biol 130:227–237PubMedGoogle Scholar
  140. 140.
    Yang X, Meyer K, Friedl A (2013) STAT5 and prolactin participate in a positive autocrine feedback loop that promotes angiogenesis. J Biol Chem 288:21184–21196PubMedCentralPubMedGoogle Scholar
  141. 141.
    Lai KP, Huang CK, Fang LY, Izumi K, Lo CW et al (2013) Targeting stromal androgen receptor suppresses prolactin-driven benign prostatic hyperplasia (BPH). Mol Endocrinol 27:1617–1631PubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  • Kathleen A. O’Leary
    • 1
    Email author
  • Michael P. Shea
    • 1
  • Linda A. Schuler
    • 1
  1. 1.Department of Comparative BiosciencesUniversity of Wisconsin–MadisonMadisonUSA

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