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The Many Faces of Prolactin in Breast Cancer

  • Wen Y ChenEmail author
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 846)

Abstract

Prolactin (PRL) is a neuroendocrine polypeptide hormone primarily produced by the lactotrophs in the anterior pituitary gland of all vertebrates. The physiological role of PRL in mammary glands is relatively certain while its role in breast tumor has been a topic of debate for over 20 years. In this review, the author attempts to briefly summarize the data coming from his laboratory in the past years, focusing on G129R, a PRL receptor (PRLR) antagonist developed by introducing a single amino acid substitution mutation into human PRL (hPRL) at position 129, and a variety of G129R derivatives. The author has proposed two novel ideas for potential use of PRL, not anti-PRL agents, as an adjuvant agent for breast cancer, making it a hormone of many faces.

Keywords

Breast Cancer Mammary Gland Breast Cancer Cell Line Breast CSCs Breast Cancer Etiology 
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.

Abbreviations

ASC

Adult stem cell

CSC

Cancer stem cell

ELISA

Enzyme-linked immunosorbent assay

GH

Growth hormone

GHR

Growth hormone receptor

hPRL

Human prolactin

HUVEC

Human umbilical vein endothelial cell

IL-2

Interleukin-2

KO

Knockout

MT

Metallothionein promoter

NRL

Neu-related-lipocalin

PRL

Prolactin

PRLR

Prolactin receptor

qPCR

Quantitative polymerase chain reaction

Notes

Acknowledgements

The author wishes to thank all of his former and current laboratory members for their contributions to this work. The author also wants to apologize to those colleagues whose important work was not cited due to either space limits or oversights. Special thanks goes to Dr. John Langenheim for his critical reading of this manuscript. The author is in debt to Dr. Nian-yi Chen for her long-time support and significant contributions both in PRL as well as in GH antagonist projects. Last but not least, the author would like to thank Cynthia Chen for her help in proofreading the manuscript.

References

  1. 1.
    Forrest P (1997) Introduction to breast cancer. In: Langdon SP, Miller WR, Berchuck A (eds) Biology of female cancers. CRC Press, LLC, pp 31–42Google Scholar
  2. 2.
    (2008) The MD Anderson Cancer Care Series: breast cancer, 2nd edn. In: KK Hunt, GL Robb, EA Strom, NT Ueno (eds) Springer Science Business Media LLC, New York, 561 p. Softcover. ISBN 978-0-387-34950-3Google Scholar
  3. 3.
    Kelly PA, Djiane J, Postel-Vinay MC, Edery M (1991) The prolactin/growth hormone receptor family. Endocri Rev 12:235–251CrossRefGoogle Scholar
  4. 4.
    Horseman ND, Zhao W, Montecino-Rodriguez E, Tanaka M, Nakashima K, Engle SJ, Smith F (1997) Defective mammopoiesis, but normal hematopoiesis, in mice with a targeted disruption of the prolactin gene. EMBO J 16:6926–6935CrossRefPubMedCentralPubMedGoogle Scholar
  5. 5.
    Ormandy CJ, Camus A, Barra J, Damotte D, Lucas B, Buteau H, Edery M, Brousse N, Babinet C, Binart N, Kelly PA (1997) Null mutation of the prolactin receptor gene produces multiple reproductive defects in the mouse. Genes Dev 15:167–178CrossRefGoogle Scholar
  6. 6.
    Ginsburg E, Vonderhaar BK (1995) Prolactin synthesis and secretion by human breast cancer cells. Cancer Res 55(12):2591–2595PubMedGoogle Scholar
  7. 7.
    Wagner KU, Rui H (2008) Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression. J Mammary Gland Biol Neoplasia 13(1):93–103. ReviewCrossRefPubMedGoogle Scholar
  8. 8.
    LaPensee EW, Ben-Jonathan N (2010) Novel roles of prolactin and estrogens in breast cancer: resistance to chemotherapy. Endocr Relat Cancer 17(2):R91–107 (Review)CrossRefPubMedGoogle Scholar
  9. 9.
    Clevenger CV, Furth PA, Hankinson SE, Schuler LA (2003) The role of prolactin in mammary carcinoma. Endocr Rev 24(1):1–27 (Review)CrossRefPubMedCentralPubMedGoogle Scholar
  10. 10.
    Cecim M, Bartke A, Yun JS, Wagner TE (1994) Expression of human, but not bovine, growth hormone genes promotes development of mammary tumors in transgenic mice. Transgenics 1:431–437Google Scholar
  11. 11.
    Wennbo H, Gebre-Medhin M, Gritli-Linde A, Ohlsson C, Isaksson OG, Tornell J (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 100:2744–2751CrossRefPubMedCentralPubMedGoogle Scholar
  12. 12.
    Arendt LM, Schuler LA (2008) Transgenic models to study actions of prolactin in mammary neoplasia. J Mammary Gland Biol Neoplasia 13(1):29–40 (Review)CrossRefPubMedGoogle Scholar
  13. 13.
    Purnell DM, Hillman EA, Heatfield BM, Trump BF (1982) Immunoreactive prolactin in epithelial cells of normal and cancerous human breast and prostate detected by the unlabeled antibody peroxidase-antiperoxidase method. Cancer Res 42:2317–2324PubMedGoogle Scholar
  14. 14.
    Manni A, Pontari M, Wright C (1985) Autocrine stimulation by prolactin of hormone-responsive breast cancer growth in culture. Endocrinology 117:2024–2043CrossRefGoogle Scholar
  15. 15.
    Mershon J, Sall W, Mitchner N, Ben-Jonathan N (1995) Prolactin is a local growth factor in rat mammary tumors. Endocrinology 136:3619–3623PubMedGoogle Scholar
  16. 16.
    Love RR, Rose DR, Surawicz TS, Newcomb PA (1991) Prolactin and growth hormone levels in premenopausal women with breast cancer and healthy women with strong family history of breast cancer. Cancer 68:1401–1405CrossRefPubMedGoogle Scholar
  17. 17.
    Peyrat JP, DeWailly D, Djiane J, Kelly PA, Vandewalle B, Bonneterre J, LeFebvre. J (1981) Total prolactin binding sites in human breast cancer biopsies. Breast Cancer Res Treat 1:369–373CrossRefPubMedGoogle Scholar
  18. 18.
    Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger C (1997) Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 138:5555–5560PubMedGoogle Scholar
  19. 19.
    Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F, Malet C, Nicolas A, Trivin C, Postel-Vinay MC, Kuttenn F, Kelly PA (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(2):667–674CrossRefPubMedGoogle Scholar
  20. 20.
    Chen WY, Wight DC, Wagner TE, Kopchick JJ (1990) Expression of a mutated bovine growth hormone gene suppresses growth of transgenic mice. Proc Natl Acad Sci USA 87:5061–5065CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Chen WY, White ME, Wagner TE, Kopchick JJ (1991) Functional antagonism between endogenous mouse growth hormone (GH) and a GH analog results in transgenic dwarf mice. Endocrinology 129:1402–1408CrossRefPubMedGoogle Scholar
  22. 22.
    Chen WY, Wight DC, Mehta BV, Wagner TE, Kopchick JJ (1991) Glycine 119 of bovine growth hormone is critical for growth promoting activity. Mol Endocrinol 5:1845–1852CrossRefPubMedGoogle Scholar
  23. 23.
    Chen WY, Chen NY, Yun J, Wagner TE, Kopchick JJ (1994) In vitro and in vivo studies of antagonists effects of human growth hormone analogs. J Biol Chem 269:15892–15897PubMedGoogle Scholar
  24. 24.
    Chen WY, Chen NY, Yun J, Wight DC, Wang XZ, Wagner TE, Kopchick JJ (1995) Amino acid residues in the third alpha-helix of growth hormone involved in growth promoting activity. Mol Endocrinol 9:292–302PubMedGoogle Scholar
  25. 25.
    Okada S, Chen WY, Wiehl P, Kelder B, Goodman HM, Guller S, Sonenberg M, Kopchick JJ (1992) A growth hormone (GH) analog can antagonize the ability of native GH to promote differentiation of 3T3-F442 A preadipocytes and to stimulate insulin-like and lipolytic activities in primary rat adipocytes. Endocrinology 130:2284–2290PubMedGoogle Scholar
  26. 26.
    Fuh G, Cunningham BC, Fukunaga R, Nagata S, Goeddel DV, Wells JA (1992) Rational design of potent antagonists to the human growth hormone receptor. Science 256:1677–1680CrossRefPubMedGoogle Scholar
  27. 27.
    DeVos A, Ultsch M, Kosslakoff AA (1992) Human growth hormone and extracellular domain of its receptor: crystal structure of the complex. Science 255:306–312CrossRefGoogle Scholar
  28. 28.
    Cunningham BC, Bass S, Fuh G, Wells JA (1990) Zinc mediation of the binding of human growth hormone to the human prolactin receptor. Science 250:1709–1712CrossRefPubMedGoogle Scholar
  29. 29.
    Luck DN, Huyer M, Gout PW, Beer CT, Smith M (1991) Single amino acid substitutions in recombinant bovine prolactin that markedly reduce its mitogenic activity in NB2 cell cultures. Mol Endocrinol 5:1880–1886CrossRefPubMedGoogle Scholar
  30. 30.
    Xu J, Sun D, Jiang J, Deng L, Zhang Y, Yu H, Bahl D, Langenheim JF, Chen WY, Fuchs SY, Frank SJ (2013) The role of prolactin receptor in GH signaling in breast cancer cells. Mol Endocrinol 27(2):266–279CrossRefPubMedCentralPubMedGoogle Scholar
  31. 31.
    Xu J, Zhang Y, Berry PA, Jiang J, Lobie PE, Langenheim JF, Chen WY, Frank SJ (2011) Growth hormone signaling in human T47D breast cancer cells: potential role for a growth hormone receptor-prolactin receptor complex. Mol Endocrinol 25(4):597–610CrossRefPubMedCentralPubMedGoogle Scholar
  32. 32.
    Yang N, Langenheim JF, Wang X, Jiang J, Chen WY, Frank SJ (2008) Activation of growth hormone receptors by growth hormone and growth hormone antagonist dimers: insights into receptor triggering. Mol Endocrinol 22(4):978–988CrossRefPubMedCentralPubMedGoogle Scholar
  33. 33.
    Clevenger CV, Gadd SL, Zheng J (2009) New mechanisms for PRLr action in breast cancer. Trends Endocrinol Metab 20(5):223–229 (Review)CrossRefPubMedGoogle Scholar
  34. 34.
    Goffin V, Struman I, Mainfroid V, Kinet S, Martial JA (1994) Evidence for a second receptor binding site on human prolactin. J Biol Chem 269:32598–32606PubMedGoogle Scholar
  35. 35.
    Kinet S, Bernichtein S, Kelly PA, Martial JA, Goffin V (1999) Biological properties of human prolactin analogs depend not only on global hormone affinity, but also on the relative affinities of both receptor binding sites. J Biol Chem 274(37):26033–26043CrossRefPubMedGoogle Scholar
  36. 36.
    Chen WY, Ramamoorthy P, Chen N, Sticca R, Wagner TE (1999) A human prolactin antagonist, hPRL-G129R, inhibits breast cancer cell proliferation through induction of apoptosis. Clin Cancer Res 5(11):3583–3593PubMedGoogle Scholar
  37. 37.
    Goffin V, Bernichtein S, Touraine P, Kelly PA (2005) Development and potential clinical uses of human prolactin receptor antagonists. Endocr Rev 26(3):400–422CrossRefPubMedGoogle Scholar
  38. 38.
    Peirce SK, Chen WY (2001) Quantification of prolactin receptor mRNA in multiple human tissues and cancer cell lines by real time RT-PCR. J Endocrinol 171(1):R1–R4CrossRefPubMedGoogle Scholar
  39. 39.
    Nitze LM, Galsgaard ED, Din N, Lund VL, Rasmussen BB, Berchtold MW, Christensen L, Panina S (2013) Reevaluation of the proposed autocrine proliferative function of prolactin in breast cancer. Breast Cancer Res Treat 142(1):31–44CrossRefPubMedCentralPubMedGoogle Scholar
  40. 40.
    Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. ReviewCrossRefPubMedGoogle Scholar
  41. 41.
    Cataldo L, Chen NY, Yuan Q, Li W, Ramamoorthy P, Wagner TE, Sticca RP, Chen WY (2000) Inhibition of oncogene STAT3 phosphorylation by a prolactin antagonist, hPRL-G129R, in T-47D human breast cancer cells. Int J Oncol 17(6):1179–1185PubMedGoogle Scholar
  42. 42.
    Ramamoorthy P, Sticca R, Wagner TE, Chen WY (2001) In vitro studies of a prolactin antagonist, hPRL-G129R in human breast cancer cells. Int J Oncol 18(1):25–32PubMedGoogle Scholar
  43. 43.
    Tomblyn S, Langenheim JF, Jacquemart IC, Holle E, Chen WY (2005) The role of human prolactin and its antagonist, G129R, in mammary gland development and DMBA-initiated tumorigenesis in transgenic mice. Int J Oncol 27(5):1381–1389PubMedGoogle Scholar
  44. 44.
    Scotti ML, Langenheim JF, Tomblyn S, Springs AE, Chen WY (2008) Additive effects of a prolactin receptor antagonist, G129R, and herceptin on inhibition of HER2-overexpressing breast cancer cells. Breast Cancer Res Treat 111(2):241–250CrossRefPubMedGoogle Scholar
  45. 45.
    Stransky B, de Souza SJ (2013) Modeling tumor evolutionary dynamics. Front Physiol 3:480CrossRefPubMedCentralPubMedGoogle Scholar
  46. 46.
    Bogorad RL, Courtillot C, Mestayer C, Bernichtein S, Harutyunyan L, Jomain JB, Bachelot A, Kuttenn F, Kelly PA, Goffin V, Touraine P (2008) Benign breast diseases study group. Identification of a gain-of-function mutation of the prolactin receptor in women with benign breast tumors. Proc Natl Acad Sci U S A 105(38):14533–14538CrossRefPubMedCentralPubMedGoogle Scholar
  47. 47.
    Beck MT, Chen NY, Franek KJ, Chen WY (2003) Prolactin antagonist-endostatin fusion protein as a targeted dual-functional therapeutic agent for breast cancer. Cancer Res 63(13):3598–3604PubMedGoogle Scholar
  48. 48.
    Zhang G, Li W, Holle L, Chen N, Chen WY (2002) A novel design of targeted endocrine and cytokine therapy for breast cancer. Clin Cancer Res 8(4):1196–1205PubMedGoogle Scholar
  49. 49.
    Langenheim JF, Chen WY (2005) Development of a prolactin receptor-targeting fusion toxin using a prolactin antagonist and a recombinant form of Pseudomonas exotoxin A. Breast Cancer Res Treat 90(3):281–293CrossRefPubMedCentralPubMedGoogle Scholar
  50. 50.
    Folkman J (1974) Tumor angiogenesis. Adv Cancer Res 19:331–358 (Review)CrossRefPubMedGoogle Scholar
  51. 51.
    Tomblyn S, Springs AE, Langenheim JF, Chen WY (2009) Combination therapy using three novel prolactin receptor antagonist-based fusion proteins effectively inhibits tumor recurrence and metastasis in HER2/neu transgenic mice. Int J Oncol 34(4):1139–1146PubMedGoogle Scholar
  52. 52.
    Rasmussen LM, Frederiksen KS, Din N, Galsgaard E, Christensen L, Berchtold MW, Panina S (2010) Prolactin and oestrogen synergistically regulate gene expression and proliferation of breast cancer cells. Endocr Relat Cancer 17(3):809–822CrossRefPubMedGoogle Scholar
  53. 53.
    Scotti ML, Langenheim JF, Tomblyn S, Springs AE, Chen WY (2008) Additive effects of a prolactin receptor antagonist, G129R, and herceptin on inhibition of HER2-overexpressing breast cancer cells. Breast Cancer Res Treat 111(2):241–250CrossRefPubMedGoogle Scholar
  54. 54.
    Yamauchi T, Yamauchi N, Ueki K, Sugiyama T, Waki H, Miki H, Tobe K, Matsuda S, Tsushima T, Yamamoto T, Fujita T, Taketani Y, Fukayama M, Kimura S, Yazaki Y, Nagai R, Kadowaki T (2000) Constitutive tyrosine phosphorylation of ErbB-2 via Jak2 by autocrine secretion of prolactin in human breast cancer. J Biol Chem 275(43):33937–33944CrossRefPubMedGoogle Scholar
  55. 55.
    Xu C, Langenheim JF, Chen WY (2012) Stromal-epithelial interactions modulate cross-talk between prolactin receptor and HER2/Neu in breast cancer. Breast Cancer Res Treat 134(1):157–169CrossRefPubMedGoogle Scholar
  56. 56.
    Wen Y, Zand B, Ozpolat B, Szczepanski MJ, Lu C, Yuca E, Carroll AR, Alpay N, Bartholomeusz C, Tekedereli I, Kang Y, Rupaimoole R, Pecot CV, Dalton HJ, Hernandez A, Lokshin A, Lutgendorf SK, Liu J, Hittelman WN, Chen WY, Lopez-Berestein G, Szajnik M, Ueno NT, Coleman RL, Sood AK (2014) Antagonism of tumoral prolactin receptor promotes autophagy-related cell death. Cell Rep 7(14):187–189Google Scholar
  57. 57.
    Coley HM (2008) Mechanisms and strategies to overcome chemotherapy resistance in metastatic breast cancer. Cancer Treat Rev 34:378–390CrossRefPubMedGoogle Scholar
  58. 58.
    Rosen JM, Jordan CT (2009) The increasing complexity of the cancer stem cell paradigm. Science 324:1670–1673CrossRefPubMedCentralPubMedGoogle Scholar
  59. 59.
    Nakshatri H, Srour EF, Badve S (2009) Breast cancer stem cells and intrinsic subtypes: controversies rage on. Curr Stem Cell Res Ther 4:50–60CrossRefPubMedGoogle Scholar
  60. 60.
    Baccelli I, Trumpp A (2012) The evolving concept of cancer and metastasis stem cells. J Cell Biol 198(3):281–293CrossRefPubMedCentralPubMedGoogle Scholar
  61. 61.
    Bonnet D, Dick JE (1997) Human acute myeloid leukemia is organized as a hierarchy that originates from a primitive hematopoietic cell. Nat Med 3(7):730–737CrossRefPubMedGoogle Scholar
  62. 62.
    Siddique HR, Saleem M (2012) Role of BMI1, a stem cell factor, in cancer recurrence and chemoresistance: preclinical and clinical evidences. Stem Cells 30(3):372–378CrossRefPubMedGoogle Scholar
  63. 63.
    Federici G, Espina V, Liotta L, Edmiston KH (2011) Breast cancer stem cells: a new target for therapy. Oncology (Williston Park) 25(1):25–28 (Review)Google Scholar
  64. 64.
    Nicolini A, Ferrari P, Fini M, Borsari V, Fallahi P, Antonelli A, Berti P, Carpi A, Miccoli P (2011) Stem cells: their role in breast cancer development and resistance to treatment. Curr Pharm Biotechnol 12(2):196–205 (Review)CrossRefPubMedGoogle Scholar
  65. 65.
    Azzi S, Bruno S, Giron-Michel J, Clay D, Devocelle A, Croce M, Ferrini S, Chouaib S, Vazquez A, Charpentier B, Camussi G, Azzarone B, Eid P (2011) Differentiation therapy: targeting human renal cancer stem cells with interleukin 15. J Natl Cancer Inst 103(24):1884–1898CrossRefPubMedGoogle Scholar
  66. 66.
    Hennighausen L, Robinson GW (2001) Signaling pathways in mammary gland development. Dev Cell 1(4):467–475CrossRefPubMedGoogle Scholar
  67. 67.
    Hinck L, Silberstein GB (2005) Key stages in mammary gland development: the mammary end bud as a motile organ. Breast Cancer Res 7(6):245–251CrossRefPubMedCentralPubMedGoogle Scholar
  68. 68.
    Al-Hajj M, Wicha MS, Benito-Hernandez A, Morrison SJ, Clarke MF (2003) Prospective identification of tumori- genic breast cancer cells. Proc Natl Acad Sci U S A 100:3983–3988CrossRefPubMedCentralPubMedGoogle Scholar
  69. 69.
    Ponti D, Costa A, Zaffaroni N, Pratesi G, Petrangolini G, Coradini D, Pilotti S, Pierotti MA, Daidone MG (2005) Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/pro- genitor cell properties. Cancer Res 65:5506–5511CrossRefPubMedGoogle Scholar
  70. 70.
    Huang EH1, Heidt DG, Li CW, Simeone DM (2007) Cancer stem cells: a new paradigm for understanding tumor progression and therapeutic resistance. Surgery 141(4):415–419CrossRefPubMedGoogle Scholar
  71. 71.
    Gökmen-Polar Y, Nakshatri H, Badve S (2011) Biomarkers for breast cancer stem cells: the challenges ahead. Biomark Med 5(5):661–671 (Review)CrossRefPubMedGoogle Scholar
  72. 72.
    Moreb JS (2008) Aldehyde dehydrogenase as a marker for stem cells. Curr Stem Cell Res Ther 3(4):237–246 (Review)CrossRefPubMedGoogle Scholar
  73. 73.
    Gupta PB, Onder TT, Jiang G, Tao K, Kuperwasser C, Weinberg RA, Lander ES (2009) Identification of selective inhibitors of cancer stem cells by high-throughput screening. Cell 138:645–659CrossRefPubMedGoogle Scholar
  74. 74.
    Fuchs D, Daniel V, Sadeghi M, Opelz G, Naujokat C (2010) Salinomycin overcomes ABC transporter-mediated multidrug and apoptosis resistance in human leukemia stem cell-like KG-1a cells. Biochem Biophys Res Commun 394:1098–1104CrossRefPubMedGoogle Scholar
  75. 75.
    Hirsch HA, Iliopoulos D, Tsichlis PN, Struhl K (2009) Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission. Cancer Res 69:7507–7511CrossRefPubMedCentralPubMedGoogle Scholar
  76. 76.
    LaPensee EW, Schwemberger SJ, LaPensee CR, Bahassi M, Afton SE, Ben-Jonathan N (2009) Prolactin confers resistance against cisplatin in breast cancer cells by activating glutathione-S-transferase. Carcinogenesis 30(8):1298–1304CrossRefPubMedCentralPubMedGoogle Scholar
  77. 77.
    Li Q, Chow AB, Mattingly RR (2010) Three-dimensional overlay culture models of human breast cancer reveal a critical sensitivity to mitogen-activated protein kinase kinase inhibitors. J Pharmacol Exp Ther 332(3):821–828CrossRefPubMedCentralPubMedGoogle Scholar
  78. 78.
    Baker BM, Chen CS (2012) Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci 125(Pt 13):3015–3024CrossRefPubMedCentralPubMedGoogle Scholar
  79. 79.
    Schyschka L, Sánchez JJ, Wang Z, Burkhardt B, Müller-Vieira U, Zeilinger K, Bachmann A, Nadalin S, Damm G, Nussler AK (2013) Hepatic 3D cultures but not 2D cultures preserve specific transporter activity for acetaminophen-induced hepatotoxicity. Arch Toxicol 87(8):1581–1593CrossRefPubMedGoogle Scholar
  80. 80.
    Tran TH, Utama FE, Lin J, Yang N, Sjolund AB, Ryder A, Johnson KJ, Neilson LM, Liu C, Brill KL, Rosenberg AL, Witkiewicz. AK, Rui H (2010) Prolactin inhibits BCL6 expression in breast cancer through a Stat5a-dependent mechanism. Cancer Res 70(4):1711–1721CrossRefPubMedCentralPubMedGoogle Scholar
  81. 81.
    Sato T, Tran TH, Peck AR, Girondo MA, Liu C, Goodman CR, Neilson LM, Freydin B, Chervoneva I, Hyslop T, Kovatich AJ, Hooke JA, Shriver CD, Fuchs S, Y., Rui H (2014) Prolactin suppresses a progestin-induced CK5-positive cell population in luminal breast cancer through inhibition of progestin-driven BCL6 expression. Oncogene 33(17):2215–2224CrossRefPubMedCentralPubMedGoogle Scholar
  82. 82.
    Russo J, Russo IH (2004) Molecular basis of breast cancer: prevention and treatment. Springer, BerlinCrossRefGoogle Scholar
  83. 83.
    Russo IH, Koszalka M, Russo J (1990) Human chorionic gonadotropin and rat mammary cancer prevention. J Natl Cancer Inst 82(15):1286–1289CrossRefPubMedGoogle Scholar
  84. 84.
    Rajkumar L, Kittrell FS, Guzman RC, Brown PH, Nandi S, Medina D (2007) Hormone-induced protection of mammary tumorigenesis in genetically engineered mouse models. Breast Cancer Res 9(1):R12CrossRefPubMedCentralPubMedGoogle Scholar
  85. 85.
    Rajkumar L, Guzman RC, Yang J, Thordarson G, Talamantes F, Nandi S (2001) Short-term exposure to pregnancy levels of estrogen prevents mammary carcinogenesis. Proc Natl Acad Sci U S A 98(20):11755–11759CrossRefPubMedCentralPubMedGoogle Scholar
  86. 86.
    Guzman RC, Yang J, Rajkumar L, Thordarson G, Chen X, Nandi S (1999) Hormonal prevention of breast cancer: mimicking the protective effect of pregnancy. Proc Natl Acad Sci U S A 96(5):2520–2525CrossRefPubMedCentralPubMedGoogle Scholar
  87. 87.
    Tekmal RR, Nair HB, Perla RP, Kirma N (2007) HER –2/neu x aromatase double transgenic mice model: the effects of aromatase overexpression on mammary tumorigenesis. J Steroid Biochem Mol Biol 106(1–5):111–118CrossRefPubMedCentralPubMedGoogle Scholar
  88. 88.
    Wennbo H, Gebre-Medhin M, Gritli-Linde A, Ohlsson C, Isaksson OG, Tornell J (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(11):2744–2751CrossRefPubMedCentralPubMedGoogle Scholar
  89. 89.
    Rose-Hellekant TA, Arendt LM, Schroeder MD, Gilchrist K, Sandgren EP, Schuler LA (2003) Prolactin induces ERalpha-positive and ERalpha-negative mammary cancer in transgenic mice. Oncogene 22(30):4664–4674CrossRefPubMedCentralPubMedGoogle Scholar
  90. 90.
    Hwang P, Guyda H, Friesen H (1972) Purification of human prolactin. J Biol Chem 247(7):1955–1958PubMedGoogle Scholar
  91. 91.
    Langenheim JF, Chen WY (2009) Improving the pharmacokinetics/pharmacodynamics of prolactin, GH, and their antagonists by fusion to a synthetic albumin-binding peptide. J Endocrinol 203(3):375–387CrossRefPubMedGoogle Scholar
  92. 92.
    Goodman G, Bercovich D (2008) Prolactin does not cause breast cancer and may prevent it or be therapeutic in some conditions. Med Hypotheses 70(2):244–251CrossRefPubMedGoogle Scholar
  93. 93.
    Felsher DW (2003) Cancer revoked: oncogenes as therapeutic targets. Nat Rev 3(5):375–380CrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of Biological SciencesClemson University, Greenville Health SystemGreenvilleUSA

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