Direct Effects of LHRH and Agonists on Human Breast Cancer Cells

  • W. R. Miller
  • W. N. Scott
  • R. Morris
  • H. M. Fraser
  • R. M. Sharpe
Part of the Biochemical Endocrinology book series (BIOEND)


The growth of the human female breast is clearly under endocrine control. In the absence of stimulatory hormones, the breast remains rudimentary whilst major development normally only occurs at times of increased hormone production such as puberty and pregnancy. It is, therefore, not surprising that certain breast cancers should also require hormones for their continued growth. Whilst polypeptide hormones are capable of influencing events within breast cancers, (Dilley and Kister, 1975, Leung and Shiu, 1981) the most convincing evidence for the involvement of endocrine agents is for steroid hormones, particularly oestrogens. This includes the observations that, a) the growth of cell lines of human breast cancer may be stimulated by oestrogen both in culture (Butler et al, 1981, Benz et al, 1983) and in immunosuppressed animals (Shafie 1980, Seibert et al, 1983); b) the administration of oestrogen to breast cancer patients with metastatic deposits in bone may cause increased urinary calcium excretion due to accelerated tumour growth (Pearson et al, 1954); c) oestrogen deprivation therapy causes regression of breast cancers in about one-third of patients with advanced disease (Henderson and Canellos, 1980); d) these effects are invariably associated with tumours which possess receptors for oestrogen (Jensen et al, 1974, McGuire et al, 1975). Endocrine intervention therefore represents a major treatment option for advanced breast cancer especially against tumours which are rich in oestrogen receptors.


Breast Cancer Luteinizing Hormone Premenopausal Woman Human Breast Cancer Cell Advanced Breast Cancer 
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  1. Amarant, T., Fridkin, M., and Koch Y., 1982, Luteinizing hormone-releasing hormone and thyrotropin-releasing hormone in human and bovine milk, Europ J Biochem, 127:647.PubMedCrossRefGoogle Scholar
  2. Bardon, S., Vignon, F., Chalbos, D., and Rochefort, H., 1985, RU 486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via the progesterone receptor, J Clin Endocrinol Metab, 60:692.PubMedCrossRefGoogle Scholar
  3. Belchetz, P.E., Plant, T.M., Nakai, Y., Keogh, E.J., and Knobil, E., 1978, Hypophyseal responses to continuous and intermittent delivery of hypothalamic gonadotrophin-releasing hormone, Science, 202:631.PubMedCrossRefGoogle Scholar
  4. Belisle, S., Guevin, J-F., Bellabarba, D., and Leloux, J-G., 1984, Luteinizing hormone-releasing hormone binds to enriched human placental membranes and stimulates in vitro the synthesis of bioactive human chorionic gonadotropin, J Clin Endocrinol Metab, 59:119.PubMedCrossRefGoogle Scholar
  5. Benz, C., Cadman, E., Givin, J., Wu, T., Amara, J., Eisenfeld, A., and Dannies, P., 1983, Tamoxifen and 5-fluoroucil in breast cancer: Cytotoxic synergism in vitro, Cancer Res., 43:5298.PubMedGoogle Scholar
  6. Bergquist, C., Nillius, S.J., Wide, L., and Lindgren, A., 1981, Endometrial patterns in women on chronic luteinizing hormone-releasing agonist treatment for contraception, Fert Steril, 36:339.Google Scholar
  7. Bergquist, C., Nillius, S.J., and Wide, L., 1982a, Long-term intranasal luteinizing hormone-releasing hormone agonist treatment for contraception in women, Fert Steril, 38:190.Google Scholar
  8. Bergquist, C., Nillius, S.J., and Wide, L., 1982b, Failure of positive feedback of oestradiol during chronic intranasal luteinizing hormone-releasing hormone agonist treatment, Clin Endocrinol, 16:147.CrossRefGoogle Scholar
  9. Bramley, T.A., Menzies, G.S., and Baird, D.T., 1985, Specific binding of LHRH and an agonist to human corpus luteum homogenates: Characterization, properties and luteal phase levels, J Clin Endocrinol Metab, 41:in press.Google Scholar
  10. Butler, W.B., Kelsey, W.H., and Goran, N., 1981, Effects of serum and insulin on the sensitivity of the human breast cancer cell line MCF-7 to estrogen and antiestrogens, Cancer Res, 41:82.PubMedGoogle Scholar
  11. Cailleau, R., Young, R., Olive, M., and Reeve, W.J., 1974, Breast tumour cell lines from pleural effusions, JNCI, 53:661.PubMedGoogle Scholar
  12. Clayton, R.N., Harwood, J.P., and Catt, K.J., 1979, Gonadotropin-releasing hormone analogue binds to luteal cells and inhibits progesterone production, Nature, 282:90.PubMedCrossRefGoogle Scholar
  13. Corbin, A., 1982, From contraception to cancer: a review of the therapeutic applications of LHRH analogues as antitumour agents, Yale J Biol Med, 55:27.PubMedGoogle Scholar
  14. Currie, A.J., Fraser, H.M., and Sharpe, R.M., 1981, Human placental receptors for luteinizing hormone releasing hormone, Biochem Biophys Res Commun, 99:332.PubMedCrossRefGoogle Scholar
  15. Dilley, W.G., and Kister, S.J., 1975, In vitro stimulation of human breast tissue by human prolactin, JNCI, 55:35.PubMedGoogle Scholar
  16. Eidne, K.A., Flanagan, C.A., and Millar, R.P., 1985, Gonadotropin-releasing hormone binding sites in human breast carcinoma, Science, in press.Google Scholar
  17. Fraser, H.M., and Sandow, J., 1985, Suppression of follicular maturation by infusion of a luteinizing hormone releasing hormone agonist starting during the luteal phase in the stumptailed macaque monkey, J Clin Endocrinol Metab, 60:579.PubMedCrossRefGoogle Scholar
  18. Furr, B.J.A., and Nicholson, R.I., 1982, Use of analogues of luteinizing hormone-releasing hormone for the treatment of cancer, J Reproduct Fertil, 64:529.CrossRefGoogle Scholar
  19. Hardt, W., and Schmidt-Gollwitzer, M., 1983, Sustained gonadal suppression in fertile women with the LHRH agonist, buserelin, Clin Endocrinol, 19:613.CrossRefGoogle Scholar
  20. Harvey, H.A., Lipton, A., and Max, D.T., 1984, LHRH analogs for human mammary carcinoma in: “LHRH and its Analogs, Contraceptive and Clinical Application”, B.H. Vickery, J.J. Nestor and E.S.E. Hafez, eds, MTP, Lancaster, p 329.CrossRefGoogle Scholar
  21. Henderson I.C., and Canellos, G.P., 1980, Cancer of the breast: the past decase, N Engl J Med, 302:17, 78.PubMedCrossRefGoogle Scholar
  22. Jensen, E.V., Mohlar, S., Gorell, T.A., and De Sombre, E.R., 1974, The role of estrophilin in oestrogen action, Vit and Horm, 32:89.CrossRefGoogle Scholar
  23. Keydar, I., Chen, L., Karby, S., Weiss, F.R., Delarea, J., Radu, M., Chaitcik, S., and Brenner, H.J., 1979, Establishment of a cell line of human breast carcinoma origin, Eur J Cancer, 15:659.PubMedGoogle Scholar
  24. Khodr, G., and Siler-Khodr, T.M., 1978, The effect of luteinizing hormone-releasing factor on human chorionic gonadotrophin secretion, Fert Steril, 30:301.Google Scholar
  25. Klijn, J.G.M. and de Jong, F.H., 1982, Treatment with a luteinizing-hormone-releasing-hormone analogue (buserelin) in premenopausal patients with metastatic breast cancer, The Lancet, i:1213.CrossRefGoogle Scholar
  26. Klijn, J.G.M., and de Jong, F.H., 1984, Long-term treatment with the LHRH-agonist buserelin (HOE 766) for metastatic breast cancer in single and combined drug regimens, in: “LHRH and its analogues”, F. Labrie, A. Belanger and A. Dupont, eds, Elsevier Science, Amsterdam, New York, p 425.Google Scholar
  27. Klijn, J.G.M., de Jong, F.H., Blankenstein, M.A., Docter, R., Alexieva-Figusch, J., Blonk-van-der Wijst, J., and Lamberts, W.S.J., 1984, Anti-tumour and endocrine effects of chronic LHRH agonist treatment (buserelin) with or without tamoxifen in premenopausal metastatic breast cancer, Breast Cancer Res and Treat, 4:209.CrossRefGoogle Scholar
  28. Lamberts, S.W.J., Timmers, J.M., Oosterom, R., Verleun, J., Rommerts, F.G., and de Jong, F.H., 1982, Testosterone secretion by cultured arrhenoblastoma cells: Suppression by a luteinizing hormone-releasing hormone agonist, J Clin Endocrinol Metab, 54:450.PubMedCrossRefGoogle Scholar
  29. Leung, C.K.H., and Shiu, R.P.C., 1981, Required presence of both estrogen and pituitary factors for the growth of human breast cancer cells in athymic nude mice, Cancer Res, 41:546.PubMedGoogle Scholar
  30. Lippman, M., 1981, Hormonal regulation of human breast cancer cells in vitro, in: “Banbury Report No 8 Hormones and Breast Cancer”, M.C. Pike, P.K. Siiteri and C.W. Welsch, eds, Cold Spring Harbor Laboratory, U.S.A., p 171.Google Scholar
  31. Lippman, M., Bolan, G., and Huff, K., 1976a, The effects of estrogens and antioestrogens on hormone-responsive human breast cancer in long-term tissue culture, Cancer Res, 36:4595.PubMedGoogle Scholar
  32. Lippman, M.E., Bolan, G., and Huff, K., 1976b, The effect of glucocorticoids and progesterone on hormone-responsive human breast cancer in long-term tissue culture, Cancer Res, 36:4602.PubMedGoogle Scholar
  33. Lippman, M.E., Bolan, G., and Huff, K., 1976c, The effects of androgens and anti-androgens on hormone-responsive human breast cancer in long-term tissue culture, Cancer Res, 36, 4610.PubMedGoogle Scholar
  34. McGuire, W.L., Pearson, O.H., and Segaloff, A., 1975, Predicting hormone responsiveness in human breast cancer, in: “Oestrogen receptors in human breast cancer”, W.L. McGuire, P.P. Carbone and E.D. Vollmer, eds, Raven Press, New York, p 17.Google Scholar
  35. Miller W.R., Scott, W.N., Morris, R., Fraser, H.M., and Sharpe, R.M., 1985, Growth of human breast cancer cells inhibited by a luteinizing hormone-releasing agonist, Cancer Res, 36:3610.Google Scholar
  36. Nicholson, R.I,, and Maynard, P.V., 1979, Anti-tumour activity of ICI 118630, a new potent luteinizing hormone-releasing hormone agonist, Brit J Cancer, 39:268.PubMedCrossRefGoogle Scholar
  37. Nicholson, R.I., Walker, K.J., Turkes, A., Turkes, A.O., Dyas, J., Blarney, R.W., Campbell, R.F., Robinson, M.R.G., and Griffiths, K., 1984, Therapeutic significance and the mechanism of action of the LHRH agonist ICI 118630 in breast and prostatic cancer, J Steroid Biochem, 20:129.PubMedCrossRefGoogle Scholar
  38. Nicholson, R.I,, Walker, K.J., Turkes, A., Dyas, J., Plowman, P.N., Williams, M., and Blarney, R.W., 1985, Endocrinological and clinical aspects of LHRH action (ICI 118630) in hormone dependent breast cancer, J Steroid Biochem, in press.Google Scholar
  39. Pearson, O.H., West, C.D., Hollander, V.P., and Treves, N.E., 1954 Valuation of endocrine therapy for advanced breast cancer, J.A.M.A., 154:234.CrossRefGoogle Scholar
  40. Petroza, E., Vilchez-Martinex, J.A., Coy, D.H., Arumura, A., and Schally, A.V., 1980, Reduction of LHRH pituitary and estradiol uterine binding sites by a superactive analog of luteinizing hormone-releasing hormone, Biochem Biophys Res Commun, 95:1056.CrossRefGoogle Scholar
  41. Popkin, R., Bramley, T.A., Currie, A., Shaw, R.W., Baird, D.T., and Fraser, H.M., 1983, Specific binding of luteinizing hormone-releasing hormone to human luteal tissue, Biochem Biophys Res Commun, 114:750.PubMedCrossRefGoogle Scholar
  42. Sandow, J., von Rechenberg, W., Jerzabek, G., and Stoll, W., 1978, Pituitary gonadotrophin-inhibition by a highly active analog of luteinizing hormone-releasing hormone, Fert Steril, 30:205.Google Scholar
  43. Schmidt-Gollwitzer, M., Hardt, W., Schmidt-Gollwitzer, K., von der Ohe, M., and Nevinng-Stickel, J., 1981, Influence of the LHRH analogue buserelin on cyclic ovarian function and on endometrium. A new approach to fertility control?, Contraception, 23:187.PubMedCrossRefGoogle Scholar
  44. Schmidt-Gollwitzer, M., Hardt, W., Schmidt-Gollwitzer, K., and von der Ohe, M., 1982, The contraceptive use of buserelin, a potent LHRH agonist: clinical and hormonal findings, in: “LHRH peptides as male and female contraceptives”, G. Zatuchni, ed, Lippincott, U.S.A., p 199.Google Scholar
  45. Seeburg, P.H., and Adelman, J.P., 1984, Characterization of cDNA for precursor of human luteinizing hormone-releasing hormone, Nature, 311:666.PubMedCrossRefGoogle Scholar
  46. Seibert, K., Shafie, S.M., Triche, T.J., Whang-Peng, J.J., O’Brien, S.J., Toney, J.H., Huff, K.K., and Lippman, M.E., 1983, Clonal variations of MCF-7 breast cancer cells in vitro and in athymic nude mice, Cancer Res, 43:2223.PubMedGoogle Scholar
  47. Seppala, M., and Wahlstrom, T., 1980, Identification of luteinizing hormone-releasing factor and alpha subunit of glycoprotein hormones in ductal carcinoma of the mammary gland, Int J Cancer, 26:267.PubMedCrossRefGoogle Scholar
  48. Shafie, S.M., 1980, Estrogen and growth of breast cancer:New evidence suggests indirect action, Science, 209:701.PubMedCrossRefGoogle Scholar
  49. Schally, A.V., Arimura, A., and Coy, A.H., 1980, Recent approaches to fertility control based on derivatives of LHRH, Vit and Horm, 38:257.CrossRefGoogle Scholar
  50. Schally, A.V., Redding, T.W., and Comaru-Schally, A.M., 1984, Potential use of analogs of LHRH in the treatment of hormone sensitive neoplasias, Cancer Treatment Reports 25th Anniversary Issue (NIH), 68:No 1.Google Scholar
  51. Sharpe, R.M., and Fraser, H.M., 1980, Leydig cell receptors for luteinizing hormone releasing hormone and its agonists and their modulation by administration or deprivation of the releasing hormone, Biochem Biophys Res Commun, 45:256.CrossRefGoogle Scholar
  52. Shiu, R.P.C., and Paterson, J.A., 1984, Alteration in cell shape, adhesion and lipid accumulation in human breast cancer cell (T-47D) by human prolactin and growth hormone, Cancer Res, 44:1178.PubMedGoogle Scholar
  53. Sundaram, K., Cao, Y-C., Wang, N-G., Bardin, C.W., Rivier, J., and Vale, W., 1981, Inhibition of the action of sex steroids by gonadotropin-releasing hormone (GnRH) agonists: a new biological effect, Life Sciences, 28:83.PubMedCrossRefGoogle Scholar
  54. Tan, L., and Rousseau, P., 1983, The chemical identity of the immuno-reactive LHRH-like peptide biosynthesized in the human placenta, Biochem Biophys Res Commun, 109:1061.CrossRefGoogle Scholar
  55. Thomas, D.B., 1983, Factors that promote the development of human breast cancer, Environmental Health Perspectives, 50:209.PubMedCrossRefGoogle Scholar
  56. Tureck, R.W., Mastroianni, L., Blasco, L., and Strauss, J.R., 1982, Inhibition of human granulosa cell progesterone secretion by a gonadotropin-releasing hormone agonist, J Clin Endocrinol Metab, 54:1078.PubMedCrossRefGoogle Scholar
  57. Wiznitzer, I., and Benz, C., 1984, Direct growth inhibiting effects of the prolactin antagonists Buserelin and Pergolide on human breast cancer, Proc Ann Am Assoc Cancer Res, 25:208.Google Scholar

Copyright information

© Plenum Press, New York 1986

Authors and Affiliations

  • W. R. Miller
    • 1
  • W. N. Scott
    • 1
  • R. Morris
    • 2
  • H. M. Fraser
    • 3
  • R. M. Sharpe
    • 3
  1. 1.University Department of Clinical SurgeryRoyal Infirmary EdinburghUK
  2. 2.Department of PathologyUniversity Medical SchoolEdinburghUK
  3. 3.MRC Unit of Reproductive BiologyEdinburghUK

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