Prolactin in Human Breast Cancer Development

  • Barbara K. Vonderhaar
Part of the Contemporary Endocrinology book series (COE)


In order to establish a role for a hormone in breast cancer (BC), three criteria must first be met: Specific receptors must be present in or on human BC cells, human BC cells must respond to the hormone as a mitogen, and a clinical response must be achieved when the hormone is prevented from binding to its receptors or following hormone ablation. In the case of estrogen, these three criteria have been met, and its role in human BC is widely accepted. However, the case for prolactin (PRL) has not been widely accepted, because the third criterion has been difficult to satisfy. Recent evidence from the author’ s and others’ laboratories has presented a possible explanation that accounts for the difficulty in establishing the third criterion: Human BC cells synthesize and secrete their own biologically active PRL. This review examines the three criteria, in order to establish the validity of a potential role of PRL in human BC, and to explore possible implications in management of the disease.


Breast Cancer Breast Cancer Mammary Gland Mammary Gland Development Prolactin Receptor 
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.


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  1. 1.
    Kelly PA, Djiane J, Postel-Vinay MC, Edery M. The prolactin/growth hormone receptor family. Endocrine Rev 1991; 12: 235–251.CrossRefGoogle Scholar
  2. 2.
    Kelly PA, Ali S, Rozakis M, Goujon L, Nagano M, Pellegrini I, et al. The growth hormone/prolactin receptor family. Rec Prog Hormone Res 1993; 48: 123–164.Google Scholar
  3. 3.
    Ali S, Edery M, Pellegrini I, Lesueur L, Paly J, Djiane J, Kelly PA. The Nb2 form of prolactin receptor is able to activate a milk protein gene promoter. Mol Endocrinol 1992; 6: 1242–1248.PubMedCrossRefGoogle Scholar
  4. 4.
    Clevenger CV, Chang WP, Ngo W, Pasha TLM, Montone KT, Tomaszewski JE. Expression of prolactin and prolactin receptor in human breast carcinoma. Am J Pathol 1995; 146: 695–705.PubMedGoogle Scholar
  5. 5.
    Lesueur L, Edery M, Ali S, Paly J, Kelly PA, Djiane J. Comparison of long and short forms of the prolactin receptor on prolactin-induced milk protein gene transcription. Proc Natl Acad Sci USA 1991; 88: 482–828.CrossRefGoogle Scholar
  6. 6.
    Berlanga JJ, Garcia-Ruiz JP, Perrot-Applanat M, Kelly PA, Edery M. The short form of the prolactin (PRL) receptor silences PRL induction of the 13-casein gene promoter. Mol Endocrinol 1997; 11: 1449–1457.PubMedCrossRefGoogle Scholar
  7. 7.
    O’Neal KD, Yu Lee L. Differential signal transduction of the short, Nb2, and long prolactin receptors. J Biol Chem 1994;269:26, 076–26, 082.Google Scholar
  8. 8.
    Das R, Vonderhaar BK. Transduction of prolactin’s growth signal through both the long and short forms of the prolactin receptor. Mol Endocrinol 1995; 9: 1750–1759.PubMedCrossRefGoogle Scholar
  9. 9.
    Codegone ML, DiCarlo R, Muccioli G, Bussolati G. Histology and cytometrics in human breast cancers assayed for the presence of prolactin receptors. Tumori 1981; 67: 549–552.PubMedGoogle Scholar
  10. 10.
    Peyrat JP, DeWailly D, Djiane J, Kelly PA, Vandewalle B, Bonneterre J, LeFebvre J. Total prolactin binding sites in human breast cancer biopsies. Breast Cancer Res Treat 1981; 1: 369–373.PubMedCrossRefGoogle Scholar
  11. 11.
    Bonneterre J, Peyrat JP, Vandewalle B, Beuscart R, Vie MC, Cappelaere P. Prolactin receptors in human breast cancer. Eur J Cancer Clin Oncol 1982; 18: 1157–1162.PubMedCrossRefGoogle Scholar
  12. 12.
    L’Hermite-Baleriaux M, Casteels S, Vokaer A, Loriaus C, Noel G, L’Hermite M. Prolactin and prolactin receptors in human breast disease. Prog Cancer Res Ther 1984; 31: 325–334.Google Scholar
  13. 13.
    Goffin V, Kelly PA. The prolactin/growth hormone receptor family: structure/function relations. J Mammary Gland Biol Neoplasia 1997; 2: 7–17.PubMedCrossRefGoogle Scholar
  14. 14.
    Reynolds C, Montone KT, Powell CM, Tomaszewski JE, Clevenger CV. Expression of prolactin and its receptor in human breast carcinoma. Endocrinology 1997; 138: 5555–5560.PubMedCrossRefGoogle Scholar
  15. 15.
    Mertani HC, Garcia-Caballero T, Lambert A, Gerard F, Palayer C, Boutin JM, et al. Cellular expression of growth hormone and prolactin receptors in human breast disorders. Int J Cancer 1998; 79: 201–211.CrossRefGoogle Scholar
  16. 16.
    Touraine P, Martini JF, Zafrani B, Durand JC, Labaille F, Malet C, et al. Increased expression of prolactin receptor gene assessed by quantitative polymerase chain reaction in human breast tumors versus normal breast tissue. J Clin Endocrinol Metab 1998; 83: 667–674.PubMedCrossRefGoogle Scholar
  17. 17.
    Ormandy CJ, Hall RE, Manning DL, Robertson JFR, Blarney RW, Kelly PA, Nicholson RI, Sutherland RL. Coexpression and cross-regulation of the prolactin receptor and sex steroid hormone receptors in breast cancer. J Clin Endocrinol Metab 1997; 82: 3692–3699.PubMedCrossRefGoogle Scholar
  18. 18.
    Rui H, Kirken RA, Farrar WL. Activation of receptor-associated tyrosine kinase JAK2 by prolactin. J Biol Chem 1994; 269: 5364–5368.PubMedGoogle Scholar
  19. 19.
    David M, Petricoin EF, Igarashi KI, Feldman GM, Finbloom DS, Lamer AC. Prolactin activates the interferon-regulated p91 transcription factor and the JAK2 kinase by tyrosine phosphorylation. Proc Natl Acad Sci USA 1994; 91: 7174–7178.PubMedCrossRefGoogle Scholar
  20. 20.
    Campbell GS, Argetsinger LS, Ihle JN, Kelly PA, Rillema JA, Carter-Su C. Activation of JAK (JAK2) tyrosine kinase by prolactin receptors in NB (NB2) cells and mouse mammary gland explants. Proc Natl Acad Sci USA 1994; 91: 5232–5236.PubMedCrossRefGoogle Scholar
  21. 21.
    Dusanter-Fourt I, Muller O, Ziemiecki A, Mayeux P, Drucker B, Djiane J, et al. Identification of JAK protein tyrosine kinases as signaling molecules for prolactin. Functional analysis of prolactin receptor and prolactin-erythropoietin receptor chimera expressed in lymphoid cells. EMBO J 1994; 13: 2538–2591.Google Scholar
  22. 22.
    Waters MJ, Daniel N, Bignon C, Djiane J. The rabbit mammary gland prolactin receptor is tyrosine phosphorylated in response to prolactin in vivo and in vitro. J Biol Chem 1995; 270: 5136–5143.PubMedCrossRefGoogle Scholar
  23. 23.
    DaSilva L, Rui H, Erwin RA, Howard OMZ, Kirken RA, Malabarba MG, et al. Prolactin recruits STAT1, STAT3 and STATS independent of conserved receptor tyrosine TYR402, TYR479, TYR515 and TYR580. Mol Cell Endocrinol 1996; 117: 131–140.PubMedCrossRefGoogle Scholar
  24. 24.
    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. EMBO J 1994; 13: 2182–2191.PubMedGoogle Scholar
  25. 25.
    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: 8831–8835.PubMedCrossRefGoogle Scholar
  26. 26.
    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 1996; 11: 179–186.CrossRefGoogle Scholar
  27. 27.
    Das R, Vonderhaar BK. Activation of raf-1, MEK and MAP kinase in prolactin responsive mammary cells. Breast Cancer Res Treat 1996; 40: 141–149.PubMedCrossRefGoogle Scholar
  28. 28.
    Darnell JE Jr, Kerr IM, Stark GR. Jak-STAT pathways and transcriptional activation in response to IFNs and other extracellular signaling proteins. Science 1994; 264: 1415–1421.PubMedCrossRefGoogle Scholar
  29. 29.
    Berlanga JJ, Vara JAF, Martin-Perez J, Garcia-Ruiz JP. Prolactin receptor is associated with c-src kinase in rat liver. Mol Endocrinol 1995; 9: 1461–1467.PubMedCrossRefGoogle Scholar
  30. 30.
    Clevenger CV, Medaglia MV. The protein tyrosine kinase p59fyn is associated with prolactin (PRL) receptor and is activated by PRL stimulation of T-lymphocytes. Mol Endocrinol 1994; 8: 674–681.PubMedCrossRefGoogle Scholar
  31. 31.
    Clevenger CV, Ngo W, Sokol DL, Luger SM, Gewirtz AM. Vav is necessary for prolactin-stimulated proliferation and is translocated into the nucleus of a T-cell line. J Biol Chem 1995;270:13, 246–13, 253.Google Scholar
  32. 32.
    Ali S, Chen Z, Lebrun J-J, Vogel W, Kharitonenkov A, Kelly P, Ullrich A. PTP1D is a positive regulator of the prolactin signal leading to (3-casein promoter activation. EMBO J 1996; 15: 135–142.PubMedGoogle Scholar
  33. 33.
    Daniel N, Waters MJ, Bignon C, Djiane J. Involvement of a subset of tyrosine kinases and phosphatases in regulation of the (3-lactoglobulin gene promoter by prolactin. Mol Cell Endocrinol 1996; 118: 25–35.PubMedCrossRefGoogle Scholar
  34. 34.
    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: 3512–3518.PubMedCrossRefGoogle Scholar
  35. 35.
    Elberg G, Rapoport MJ, Vashdi-Elberg D, Gertler A, Scechter Y. Lactogenic hormones rapidly activate p21 ras/mitogen-activated protein kinase in Nb2–11C rat lymphoma cells. Endocrine 1996; 4: 65–71.PubMedCrossRefGoogle Scholar
  36. 36.
    Clevenger CV, Torigoe T, Reed JC. Prolactin induces rapid phosphorylation and activation of prolactin receptor-associated RAF-1 kinase in a T-cell line. J Biol Chem 1994; 269: 5559–5565.PubMedGoogle Scholar
  37. 37.
    Buckley AR, Rao YP, Buckley DJ, Gout PW. Prolactin-induced phosphorylation and nuclear translocation of MAP kinase in Nb2 lymphoma cells. Biochem Biophys Res Commun 1994; 204: 1158–1164.PubMedCrossRefGoogle Scholar
  38. 38.
    Ganguli S, Hu L, Menke P, Collier RJ, Gertler A. Nuclear accumulation of multiple protein kinases during prolactin-induced proliferation of Nb2 rat lymphoma cells. J Cell Physio11996; 167: 251–260.Google Scholar
  39. 39.
    Rillema JA, Wing LY, Foley KA. Effects of phospholipases on ornithine decarboxylase activity in mammary gland explants from midpregnancy mice. Endocrinology 1983; 113: 2024–2028.PubMedCrossRefGoogle Scholar
  40. 40.
    Banerjee R, Vonderhaar BK. Prolactin induced protein kinase C activity in a mouse mammary epithelial cell line NOG-8. Mol Cell Endocrinol 1992; 90: 61–67.PubMedCrossRefGoogle Scholar
  41. 41.
    Waters SB, Rillema JA. Role of protein kinase C in the prolactin-induced responses in mouse mammary gland explants. Mol Cell Endocrinol 1989; 63: 159–166.PubMedCrossRefGoogle Scholar
  42. 42.
    Alsakkaf KA, Dobson PRM, Brown BL. Activation of phosphatidylinositol 3-kinase by prolactin in Nb2 cells. Biochem Biophys Res Commun 1996; 221: 779–784.CrossRefGoogle Scholar
  43. 43.
    VanderKuur J, Allevato G, Billestrup N, Norstedt G, Carter-Su C. Growth hormone-promoted tyrosyl phosphorylation of SHC proteins and SHC association with Grb2. J Biol Chem 1995; 270: 7587–7593.PubMedCrossRefGoogle Scholar
  44. 44.
    Das R, Vonderhaar BK. Involvement of SHC, Grb2, Sos and ras in prolactin signal transduction in mammary cells. Oncogene 1996; 13: 1139–1145.PubMedGoogle Scholar
  45. 45.
    David M, Petricoin E III, Benjamin C, Pine R, Weber MJ, Lamer AC. Requirement for MAP Kinase (ERK2) activity in interferon a-and interferon 13-stimulated gene expression through STAT proteins. Science 1995; 269: 1721–1723.PubMedCrossRefGoogle Scholar
  46. 46.
    Zabala MT, Garcia-Ruiz JP. Regulation of expression of the messenger ribonucleic acid encoding the cytosolic form of phosphoenolpyruvate carboxykinase in liver and small intestine of lactating rats. Endocrinology 1989; 125: 2587–2593.PubMedCrossRefGoogle Scholar
  47. 47.
    Buckley AR, Buckley DJ, Leff MA, Hoover DS, Magnuson NS. Rapid induction of pim-1 expression by prolactin and interleukin-2 in rat Nb2 lymphoma cells. Endocrinology 1995; 136: 5252–5259.PubMedCrossRefGoogle Scholar
  48. 48.
    Stevens AN, Wang Y, Sieger KA, Lu H-F, Yu-Lee LY. Biphasic transcription regulation of the interferon regulatory factor-1 gene by prolactin: involvement of y-interferon-activated sequence and stat-related proteins. Mol Endocrinol 1995; 9: 513–525.PubMedCrossRefGoogle Scholar
  49. 49.
    Musgrove EA, Hui R, Sweeney KJE, Watts CKW, Sutherland RL. Cyclins and breast cancer. J Mammary Gland Biol Neoplasia 1996; 1: 153–162.PubMedCrossRefGoogle Scholar
  50. 50.
    Sicinski P, Donaher JL, Parker SB, Li T, Fazeli A, Gardner H, et al. Cyclin DI provides a link between development and oncogenesis in the retina and breast. Cell 1995; 82: 621–630.PubMedCrossRefGoogle Scholar
  51. 51.
    Hosokawa Y, Onga T, Nakashima K. Induction of D2 and D3 cyclin-encoding genes during promotion of the G1/S transition by prolactin in rat Nb2 cells. Gene 1994; 147: 249–252.PubMedCrossRefGoogle Scholar
  52. 52.
    Vonderhaar BK. Prolactin: transport function and receptors in mammary gland development and differentiation. In: Neville MC, Daniel CW, ed. The Mammary Gland. Plenum, New York, 1987, pp. 383–438.Google Scholar
  53. 53.
    Das R, Vonderhaar BK. Prolactin as a mitogen in mammary cells. J Mammary Gland Biol Neoplasia 1997; 2: 29–39.PubMedCrossRefGoogle Scholar
  54. 54.
    Vonderhaar BK. Hormones and growth factors in mammary gland development. In: Veneziale CM, ed. Control of Cell Growth and Proliferation. Van Nostrand, New York, 1984, pp. 11–33.Google Scholar
  55. 55.
    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: 6926–6935.PubMedCrossRefGoogle Scholar
  56. 56.
    Nagasawa H, Miur K, Niki K, Namiki H. Interrelationship between prolactin and progesterone in normal mammary gland growth in SHN virgin mice. Exp Clin Endocrinol 1985; 86: 357–360.PubMedCrossRefGoogle Scholar
  57. 57.
    Muldoon TG. Interplay between estradiol and prolactin in the regulation of steroid hormone receptor levels, nature, and functionality in normal mouse mammary tissue. Endocrinology 1981; 109: 1339–1346.PubMedCrossRefGoogle Scholar
  58. 58.
    Muldoon TG. Prolactin mediation of estrogen-induced changes in mammary tissue estrogen and progesterone receptors. Endocrinology 1987; 121: 141–149.PubMedCrossRefGoogle Scholar
  59. 59.
    Vonderhaar BK, Bhattacharjee M. The mammary gland: a model for hormonal control of differentiation and preneoplasia. In: Mihich E, ed. Biological Responses in Cancer, vol. 4. Plenum, New York, 1985, pp. 125–159.Google Scholar
  60. 60.
    Muhlbock O, Boot LM. Induction of mammary cancer in mice without the mammary tumor agent by isografts of hypophyses. Cancer Res 1959; 19: 402–412.PubMedGoogle Scholar
  61. 61.
    Boyns AR, Buchan R, Cole EN, Forrest APM, Griffiths K. Basal prolactin blood levels in three strains of rat with differing incidence of 7,12-dimethylbenzanthracene-induced mammary tumors in rats. Eur J Cancer 1973; 9: 169–171.PubMedGoogle Scholar
  62. 62.
    Mershon J, Sall W, Mitchner N, Ben-Jonathan N. Prolactin is a local growth factor in rat mammary tumors. Endocrinology 1995; 136: 3619–3623.PubMedCrossRefGoogle Scholar
  63. 63.
    Welsch CW, Gribler C. Prophylaxis of spontaneously developing mammary carcinoma in C3H/HeJ female mice by suppression of prolactin. Cancer Res 1973; 33: 2939–2946.PubMedGoogle Scholar
  64. 64.
    Welsch CW, Nagasawa H. Prolactin and murine mammary tumorigenesis: a review. Cancer Res 1977; 37: 951–963.PubMedGoogle Scholar
  65. 65.
    Holtkamp W, Nagel GA, Wander HE, Rauschecker HF, VonHeyden D. Hyperprolactenemia is an indicator of progressive disease and poor prognosis in advanced breast cancer. Int J Cancer 1984; 34: 323–328.PubMedCrossRefGoogle Scholar
  66. 66.
    Strungs I, Gray RA, Rigby HB, Strutton G. Two case reports of breast carcinoma associated with prolactinoma. Pathology 1997; 29: 320–323.PubMedCrossRefGoogle Scholar
  67. 67.
    Biswas R, Vonderhaar BK. Role of serum in prolactin responsiveness of MCF-7 human breast cancer cells in long term tissue culture. Cancer Res 1987; 47: 3509–3514.PubMedGoogle Scholar
  68. 68.
    Love RR, Rose DP. Elevated bioactive prolactin in women at risk for familial breast cancer. Eur J Cancer Clin Oncol 1985; 21: 1553, 1554.Google Scholar
  69. 69.
    Love RR, Rose DR, Surawicz TS, Newcomb PA. Prolactin and growth hormone levels in premenopausal women with breast cancer and healthy women with a strong family history of breast cancer. Cancer 1991; 68: 1401–1405.PubMedCrossRefGoogle Scholar
  70. 70.
    Haus E, Lakatua DJ, Halberg F, Halberg E, Cornelissen G, Sackett LL, et al. Chronobiological studies of plasma prolactin in women in Kyushu, Japan and Minnesota, USA. J Clin Endocrinol Metab 1980; 51: 632–640.PubMedCrossRefGoogle Scholar
  71. 71.
    Holdaway IM, Mason BH, Gibbs EE, Rajasoorya C, Lethaby A, Hopkins KD, et al. Seasonal variation in the secretion of mammotrophic hormones in normal women and women with previous breast cancer. Breast Cancer Res Treat 1997; 42: 15–22.PubMedCrossRefGoogle Scholar
  72. 72.
    Bhatavdekar JM, Patel DD, Vora HH, Ghosh N, Shah NG, Karelia NH, et al. Node-positive breast cancer: prognostic significance of the plasma prolactin compared with steroid receptors and clinico-pathological features. Oncol Rep 1994; 1: 841–845.PubMedGoogle Scholar
  73. 73.
    Patel DD, Bhatavdekar JM, Chikhlikar PR, Ghosh N, Suthar TP, Shah NG, Mehta RH, Balar DB. Node negative breast carcinoma: hyperprolactinemia and/or overexpression of p53 as an independent predictor of poor prognosis compared to newer and established prognosticators. J Surg Oncol 1996; 62: 86–92.PubMedCrossRefGoogle Scholar
  74. 74.
    Lissoni P, Barni S, Cazzaniga M, Ardizzoia A, Rovelli F, Tancici G, Brivio F, Frigerio F. Prediction of recurrence in operable breast cancer by postoperative changes in prolactin secretion. Oncology 1995; 52: 439–442.PubMedCrossRefGoogle Scholar
  75. 75.
    Barni S, Lissoni P, Brivio F, Fumagalli L, Merlini D, Cataldo M, Rovelli F, Tancini G. Serum levels of insulin-like growth factor-I in operable breast cancer in relation to the main prognostic variables and their perioperative changes in relation to those of prolactin. Tumori 1994; 80: 212–215.PubMedGoogle Scholar
  76. 76.
    Purnell DM, Hillman EA, Heatfield BM, Trump BF. Immunoreactive prolactin in epithelial cells of normal and cancerous human breast and prostate detected by the unlabeled antibody peroxidase-antiperoxidase method. Cancer Res 1982; 42: 2317–2324.PubMedGoogle Scholar
  77. 77.
    Agarwal PK, Tandon S, Agarwal AK, Kumar S. Highly specific sites of prolactin binding in benign and malignant breast disease. Indian J Exper Biol 1989; 27: 1035–1038.Google Scholar
  78. 78.
    Wang DY, Hampson S, Kwa HG, Moore JW, Bulbrook RD, Fentiman IS, et al. Serum prolactin levels in women with breast cancer and their relationship to survival. Eur J Cancer Clin Oncol 1986; 22: 487–492.PubMedCrossRefGoogle Scholar
  79. 79.
    Ingram DM, Nottage EM, Roberts AN. Prolactin and breast cancer risk. Med J Aust 1990; 153: 469–473.PubMedGoogle Scholar
  80. 80.
    Henson JC, Coune A, Staquet M. Clinical trial of 2-Br-a-ergocryptine (CB154) in advanced breast cancer. Eur J Cancer 1972; 8: 155, 156.Google Scholar
  81. 81.
    Pearson OH, Manni A. Hormonal control of breast cancer growth in women and rats. In: Martini L, James VHT, ed. Current Topics in Experimental Endocrinology. Academic, New York, 1978, pp. 75–92.Google Scholar
  82. 82.
    Manni A, Boucher AE, Demers LM, Harvey HA, Lipton A, Simmonds MA, Bartholomew M. Endocrine effects of combined somatostatin analog and bromocriptine therapy in women with advanced breast cancer. Breast Cancer Res Treat 1989; 14: 289–298.PubMedCrossRefGoogle Scholar
  83. 83.
    Anderson E, Ferguson JE, Morten H, Shalet SM, Robinson EL, Howell A. Serum immunoreactive and bioactive lactogenic hormones in advanced breast cancer patients treated with bromocriptine and octeotide. Eur J Cancer 1993; 29A: 209–217.CrossRefGoogle Scholar
  84. 84.
    Salih H, Brander W, Flax H, Hobbs JR. Prolactin dependence in human breast cancers. Lancet 1972; 2: 1103–1105.PubMedCrossRefGoogle Scholar
  85. 85.
    Welsch CW, Iturri GC, Brennan MJ. DNA synthesis of human, mouse, and rat mammary carcinomas in vitro: influence of insulin and prolactin. Cancer 1976; 38: 1272–1281.PubMedCrossRefGoogle Scholar
  86. 86.
    Peyrat JP, Djiane J, Bonneterre J, Vandewalle B, Vennin P, Delobelle A, Depadt G, Lefebvre J. Stimulation of DNA synthesis by prolactin in human breast tumor explants. Relation to prolactin receptors. Anticancer Res 1984; 4: 257–261.PubMedGoogle Scholar
  87. 87.
    Calaf G, Garrido F, Moyano C, Rodriguez R. Influence of hormones on DNA synthesis of breast tumors in culture. Breast Cancer Res Treat 1986; 8: 223–232.PubMedCrossRefGoogle Scholar
  88. 88.
    Burke RE, Gaffney EV. Prolactin can stimulate general protein synthesis in human breast cancer cells (MCF-7) in long-term culture. Life Sci 1978; 23: 901–906.PubMedCrossRefGoogle Scholar
  89. 89.
    Wilson GD, Woods KL, Walker RA, Howell A. Effect of prolactin on lactalbumin production by normal and malignant breast tissue in organ culture. Cancer Res 1980; 40: 486–489.PubMedGoogle Scholar
  90. 90.
    Malarkey WB, Kennedy M, Allred LE, Milo G. Physiological concentrations of prolactin can promote the growth of human breast tumor cells in culture. J Clin Endocrinol Metab 1983; 56: 673–677.PubMedCrossRefGoogle Scholar
  91. 91.
    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: 1669–1672.PubMedGoogle Scholar
  92. 92.
    Shiu RP, Paterson JA. Alterations of cell shape, adhesion, and lipid accumulation in human breast cancer cells (T-47D) by human prolactin and growth hormone. Cancer Res 1984; 44: 1178–1186.PubMedGoogle Scholar
  93. 93.
    Shafie SM, Grantham FH. Role of hormones in the growth and regression of human breast cancer cells (MCF-7) transplanted into athymic nude mice. J Natl Cancer Inst 1981; 67: 51–56.PubMedGoogle Scholar
  94. 94.
    McManus MJ, Welsch CW. The effect of estrogen, progesterone, thyroxine, and human placental lactogen on DNA synthesis of human breast ductal epithelium maintained in athymic nude mice. Cancer 1984; 54: 1920–1927.PubMedCrossRefGoogle Scholar
  95. 95.
    Vonderhaar BK. Prolactin: the forgotten hormone of human breast cancer. Pharmacol Ther 1998; 79: 169–178.PubMedCrossRefGoogle Scholar
  96. 96.
    Das R, Ginsburg E, Vonderhaar BK. Tamoxifen as an antilactogen in human breast cancer cells, In: Rao RS, Deo MG, Sanghvi LD, Mittra I, ed. Proceedings of the International Cancer Congress. Monduzzi Editore, Bologna, 1994, pp. 1487–1491.Google Scholar
  97. 97.
    Lemus-Wilson A, Kelly PA, Blask DE. Melatonin blocks the stimulatory effects of prolactin on human breast cancer cell growth in culture. Br J Cancer 1995; 72: 1435–1440.PubMedCrossRefGoogle Scholar
  98. 98.
    Ben-Jonathan N, Mershon JL, Allen DL, Steinmetz RW. Extrapituitary prolactin: distribution, regulation, functions, and clinical aspects. Endocr Rev 1996; 17: 639–669.PubMedGoogle Scholar
  99. 99.
    Lachelin GCL, Yen SSC, Alksne JF. Hormonal changes following hypophysectomy in humans. Obstet Gynecol 1977; 50: 333–339.PubMedGoogle Scholar
  100. 100.
    Sinha YN. Structural variants of prolactin: occurrence and physiological significance. Endocr Rev 1995; 16: 354–369.PubMedGoogle Scholar
  101. 101.
    Clevenger CV, Russell DH, Appasamy PM, Prystowsky MB. Regulation of IL-2-driven T-lymphocyte proliferation by prolactin. Proc Natl Acad Sci USA 1990; 87: 6460–6464.PubMedCrossRefGoogle Scholar
  102. 102.
    Gellerson B, Kempf R, Teglmann R, DiMattia GE. Nonpituitary human prolactin gene transcription is independent of pit-1 and differentially controlled in lymphocytes and in endometrial stroma. Mol Endocrinol 1994; 8: 356–373.CrossRefGoogle Scholar
  103. 103.
    Richards RG, Hartman SM. Human dermal fibroblast cells express prolactin in vitro. J Invest Dermatol 1996; 106: 1250–1255.PubMedCrossRefGoogle Scholar
  104. 104.
    Vonderhaar BK. Prolactin in development of the mammary gland and reproductive tract. In: Dickson RB, Salomon DS, ed. Hormones and Growth Factors in Development and Neoplasia. Wiley-Liss, New York, 1998, pp. 193–206.Google Scholar
  105. 105.
    Nevalainen MJ, Valve EM, Ingleton PM, Nurmi M, Martikainen PM, Harkonen PL. Prolactin and prolactin receptors are expressed and functioning in human prostate. J Clin Invest 1997; 99: 618–627.PubMedCrossRefGoogle Scholar
  106. 106.
    Steinmetz RW, Grant AL, Malven PV. Transcription of prolactin gene in milk secretory cells of the rat mammary gland. J Endocrinol 1993; 36: 271–276.CrossRefGoogle Scholar
  107. 107.
    Kurtz A, Bristol LA, Toth BE, Lazar-Wesley E, Takacs L, Kacsoh B. Mammary epithelial cells of lactating rats express prolactin messenger ribonucleic acid. Biol Reproduction 1993; 48: 1095–1103.CrossRefGoogle Scholar
  108. 108.
    LeProvost F, Leroux C, Martin P, Gaye P, Djiane J. Prolactin gene expression in ovine and caprine mammary gland. Neuroendocrinology 1994; 60: 305–313.CrossRefGoogle Scholar
  109. 109.
    Ginsburg E, Vonderhaar BK. Prolactin synthesis and secretion by human breast cancer cells. Cancer Res 1995; 55: 2591–2595.PubMedGoogle Scholar
  110. 110.
    Ginsburg E, Das R, Vonderhaar BK. Prolactin: an autocrine growth factor in the mammary gland. In: Wilde CJ, Peaker M, Taylor E, eds. Biological Signalling in the Mammary Gland. Hannah Institute, Ayr, Scotland, 1997, pp. 47–58.Google Scholar
  111. 111.
    Bancroft FC, Tashjian AH. Growth in suspension culture of rat pituitary cells which produce growth hormone and prolactin. Exp Cell Res 1971; 64: 125–128.PubMedCrossRefGoogle Scholar
  112. 112.
    Tanaka T, Shiu RPC, Gout PW, Beer CT, Noble RL, Friesen HG. New sensitive and specific bioassay for lactogenic hormones: measurement of prolactin and growth hormone in human serum. J Clin Endocrinol Metab 1980; 51: 1058–1063.PubMedCrossRefGoogle Scholar
  113. 113.
    Emanuele NV, Jurgens JK, Halloran MM, Tentler JJ, Lawerence AM, Kelley MR. The rat prolactin gene is expressed in brain tissue: detection of normal and alternatively spliced prolactin messenger RNA. Mol Endocrinol 1992; 6: 35–42.PubMedCrossRefGoogle Scholar
  114. 114.
    Shaw-Bruha CM, Pirrucello SJ, Shull JD. Expression of the prolactin gene in normal and neoplastic human breast tissues and human mammary cell lines: promoter usage and alternative mRNA splicing. Breast Cancer Res Treat 1997; 4: 243–253.CrossRefGoogle Scholar
  115. 115.
    Markoff E, Sigel MB, Lacour N, Seavey BK, Friesen HG, Lewis UJ. Glycosylation selectively alters the biological activity of prolactin. Endocrinology 1988; 123: 1303–1306.PubMedCrossRefGoogle Scholar
  116. 116.
    Lewis UL, Singh RNP, Lewis LJ. Two forms of glycosylated prolactin have different pigeon crop sac-stimulating activities. Endocrinology 1989; 124: 1558–1563.PubMedCrossRefGoogle Scholar
  117. 117.
    Walker AM. Phosphorylated and nonphosphorylated prolactin isoforms. Trends Endocrinol Metab 1994; 5: 195–200.PubMedCrossRefGoogle Scholar
  118. 118.
    Wicks JR, Brooks CL. Biological activity of phosphorylated and dephosphorylated bovine prolactin. Mol Cell Endocrinol 1995; 112: 223–229.PubMedCrossRefGoogle Scholar
  119. 119.
    Pellegrini I, Lebrun JJ, Ali S, Kelly PA. Expression of prolactin and its receptors in human lymphoid cells. Mol Endocrinol 1992; 6: 1023–1031.PubMedCrossRefGoogle Scholar
  120. 120.
    Sinha YN, DePaolo LV, Haro LS, Singh RNP, Jacobsen BP, Scott KE, Lewis UJ. Isolation and biochemical properties of four forms of glycosylated porcine prolactin. Mol Cell Endocrinol 1991; 80: 203–213.PubMedCrossRefGoogle Scholar
  121. 121.
    Hoffman T, Penel C, Ronin C. Glycosylation of human prolactin regulates hormone bioactivity and metabolic clearance. J Endocrinol Invest 1993; 16: 807–816.Google Scholar
  122. 122.
    Price AE, Loginenko KB, Higgins EA, Cole ES, Richards S. Studies on the microheterogeneity and in vitro activity of glycosylated and nonglycosylated recombinant human prolactin separated using a novel purification process. Endocrinology 1995; 136: 4827–4833.PubMedCrossRefGoogle Scholar
  123. 123.
    Young KH, Buhi WC, Horseman N, Davis J, Kraeling R, Linzer D, Bozer FW. Biological activities of glycosylated and nonglycosylated porcine prolactin. Mol Cell Endocrinol 1990; 71: 155–162.PubMedCrossRefGoogle Scholar
  124. 124.
    Lkhider M, Delpal S, Olivier-Bousquet M. Rat prolactin in serum, milk and mammary tissue: characterization and intracellular localization. Endocrinology 1996; 137: 4969–4979.PubMedCrossRefGoogle Scholar
  125. 125.
    Wong VLY, Compton MM, Witorsch RJ. Proteolytic modification of rat prolactin by subcellular fractions of the lactating rat mammary gland. Biochim Biophys Acta 1986; 881: 167–175.PubMedCrossRefGoogle Scholar
  126. 126.
    Baldocchi RA, Tan L, Horn YK, Nicoll CS. Comparison of the ability of normal mouse mammary tissues and mammary adenocarcinoma to cleave rat prolactin. Proc Soc Exp Biol Med 1995; 208: 283–287.PubMedGoogle Scholar
  127. 127.
    Ferrara N, Clapp C, Weiner R. The 16K fragment of prolactin specifically inhibits basal and fibroblast growth factor stimulated growth of capillary endothelial cells. Endocrinology 1991; 129: 896–900.PubMedCrossRefGoogle Scholar
  128. 128.
    D’ Angelo G, Struman I, Martial J, Weiner RI. Activation of mitogen-activated protein kinases by vascular endothelial growth factor and basic fibroblast growth factor in capillary endothelial cells is inhibited by the antiangiogenic factor 16-kDa N-terminal fragment of prolactin. Proc Natl Acad Sci USA 1995; 92: 6374–6378.PubMedCrossRefGoogle Scholar
  129. 129.
    Yoshiji H, Harris SR, Thorgeirsson UP. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res 1997; 57: 3924–3928.PubMedGoogle Scholar
  130. 130.
    Fan G, Rillema JA. Prolactin stimulation of protein kinase C in isolated mouse mammary gland nuclei. Horm Metab Res 1993; 25: 564–568.PubMedCrossRefGoogle Scholar
  131. 131.
    Fuh G, Cunningham BCRF, Nagata S, Goeddel DV, Wells JA. Rational design of potent antagonists to the human growth hormone receptor. Science 1992; 256: 1677–1679.PubMedCrossRefGoogle Scholar
  132. 132.
    Fuh G, Colosi P, Wood WI, Wells JA. Mechanism-based design of prolactin receptor antagonists. J Biol Chem 1993; 268: 5376–5381.PubMedGoogle Scholar
  133. 133.
    Fuh G, Wells JA. Prolactin receptor antagonists that inhibit the growth of breast cancer cell lines. J Biol Chem 1995;270:13, 133–13, 137.Google Scholar
  134. 134.
    Dattani MT, Hindmarsh PC, Brook GD, Robinson ICAF, Kopchick JJ, Marshall NJ. G 120R, a human growth hormone antagonist, shows zinc-dependent agonist and antagonist activity on Nb2 cells. J Biol Chem 1995; 270: 9222–9226.PubMedCrossRefGoogle Scholar
  135. 135.
    Mode A, Tollet P, Wells T, Carmignac DF, Clark RG, Chen WY, Kopchick JJ, Robinson ICAF. The human growth hormone (hGH) antagonist G120RhGH does not antagonize GH in the rat but has paradoxical agonist activity, probably via the prolactin receptor. Endocrinology 1996; 137: 447–454.PubMedCrossRefGoogle Scholar
  136. 136.
    Vonderhaar BK, Banerjee R. Is tamoxifen also an antilactogen? Mol Cell Endocr 1991; 79: 0159–0163.CrossRefGoogle Scholar
  137. 137.
    Hawkins RA, Roberts MM, Forest APM. Estrogen receptors and breast cancer: current status. BrJ Surg 1980; 67: 153–169.CrossRefGoogle Scholar
  138. 138.
    Fun BJA, Jordan VC. The pharmacology and clinical uses of tamoxifen. Pharmac Ther 1984; 25: 127–205.CrossRefGoogle Scholar
  139. 139.
    Nolvadex Adjuvant Trial Organization. Controlled trial of tamoxifen as single adjuvant agent in management of early breast cancer. Lancet 1985;i:836–839.Google Scholar
  140. 140.
    Sutherland RL, Watts CKW, Hall RE, Ruenitz PC. Mechanism of growth inhibition by nonsteroidal antioestrogens in human breast cancer cells. J Steroid Biochem 1987; 27: 891–897.PubMedCrossRefGoogle Scholar
  141. 141.
    Green MD, Whybourne AM, Taylor IW, Sutherland RL. Effects of antioestrogens on the growth and cell cycle kinetics of cultured human mammary carcinoma cells. In: Sutherland RL, Jordan VC, ed. Non-Steroidal Antiestrogens: Molecular Pharmacology and Antitumor Actions. Academic, New York, 1981, pp. 397–412.Google Scholar
  142. 142.
    Chouvet C, Vicard E, Frappart L, Falette N, Lefebvre MF, Saez S. Growth inhibitory effect of 4hydroxy-tamoxifen on the BT-20 mammary cancer cell line. J Steroid Biochem 1988; 31: 655–663.PubMedCrossRefGoogle Scholar
  143. 143.
    Pollak M, Constantino J, Polychronakas C, Blauer HG, Guyda H, Redmond C, Fisher B, Margolese R. Effect of tamoxifen on serum insulin-like growth factor I levels of stage I breast cancer patients. J Natl Cancer Inst 1990; 82: 1693–1697.PubMedCrossRefGoogle Scholar
  144. 144.
    O’Brian CA, Liskamp RM, Solomon DH, Weinstein IB. Inhibition of protein kinase C by tamoxifen. Cancer Res 1985; 45: 2462–2465.PubMedGoogle Scholar
  145. 145.
    Das R, Biswas R, Vonderhaar BK. Characteristics of the antilactogen binding site in mammary gland membranes. Mol Cell Endocrinol 1993; 98: 1–8.PubMedCrossRefGoogle Scholar
  146. 146.
    Sutherland RL, Foo MS. Differential binding of antiestrogen by rat uterine and chick oviduct cytosol. Biochem Biophys Res Commun 1979; 91: 183–191.PubMedCrossRefGoogle Scholar
  147. 147.
    Sutherland RL, Murphy LC, Foo MS, Green MD, Whybourne AM, Krozowski ZS. High-affinity anti-oestrogen binding sites distinct from the oestrogen receptor. Nature 1980; 288: 273–275.PubMedCrossRefGoogle Scholar
  148. 148.
    Gulino A, Pasqualini JR. Heterogeneity of binding sites for tamoxifen and tamoxifen derivatives in estrogen target and non-target fetal organs of guinea pig. Cancer Res 1982; 42: 1913–1921.PubMedGoogle Scholar
  149. 149.
    Mehta RG, Cerny WL, Moon RC. Distribution of antiestrogen-specific binding sites in normal and neoplastic mammary gland. Oncology 1984; 41: 387–392.PubMedCrossRefGoogle Scholar
  150. 150.
    Faye JC, Fargin A, Valette A, Bayard F. Antiestrogens, different sites of action than the estrogen receptor? Hormone Res 1987; 28: 202–211.PubMedCrossRefGoogle Scholar
  151. 151.
    Das R, Vonderhaar BK. Tamoxifen inhibits prolactin signal transduction in estrogen receptor negative NOG-8 mammary epithelial cells. Cancer Lett 1997; 116: 41–46.PubMedCrossRefGoogle Scholar
  152. 152.
    Biswas R, Vonderhaar BK. Tamoxifen inhibition of prolactin action in the mouse mammary gland. Endocrinology 1991; 128: 532–538.PubMedCrossRefGoogle Scholar
  153. 153.
    Biswas R, Vonderhaar BK. Antiestrogen inhibition of prolactin induced growth of the Nb2 rat lymphoma cell line. Cancer Res 1989; 49: 6295–6299.PubMedGoogle Scholar
  154. 154.
    Vonderhaar BK. Prolactin and breast cancer: the new chapter. Women Cancer 1999; 1: 7–20.Google Scholar

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© Humana Press Inc., Totowa, NJ 2000

Authors and Affiliations

  • Barbara K. Vonderhaar

There are no affiliations available

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