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Antiprogestin-progesterone interactions

  • H. Michna
  • K.-H. Fritzemeier
  • K. Parczyk
  • Y. Nishino
  • M. R. Schneider
Part of the Cancer Treatment and Research book series (CTAR, volume 83)

Abstract

It was more than a decade ago that in 1889 Schinzinger was the first to propose that ovariectomy may be an effective treatment for breast cancer [1,2]. Until today the available treatment strategies for hormone-dependent breast cancer have mainly been based on estrogen-ablative principles, and improvements in the therapy for breast cancer are still sorely needed. A totally different strategy utilizes progesterone antagonists: This class of compounds targets the progesterone receptor in mammary carcinomas and therefore does not represent another enzyme or receptor blockade of estrogen action.

Keywords

Progesterone Receptor Mammary Carcinoma Medroxyprogesterone Acetate Progesterone Antagonist T47D Human Breast Cancer Cell 
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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References

  1. 1.
    Schinzinger F (1889) Über Carcinoma Mammae. In Verh Dtsch Ges Chirurgie. Berlin: Hirschwald Verlag, Chap 18.Google Scholar
  2. 2.
    Beatson GT, Edin MD (1896) On the treatment of inoperable cases of carcinoma of the mamma: Suggestions for a new method of treatment, with illustrative cases. Lancet 18: 107–108.Google Scholar
  3. 3.
    Herrmann W, Wyss R, Riondel A, Philibert D, Teutsch G, Sakiz E, Baulieu EE (1982) The effects of an antiprogesterone steroid in women: Interruption of the menstrual cycle and of early pregnancy. C R Acad Sci Paris 294: 933–938.Google Scholar
  4. 4.
    Kloosterboer HJ, Deckers GHJ, Van der Heuvel MJ, Loozen HJJ (1988) Screening of antiprogestagens by receptor studies and bioassays. J Steroid Biochem 31: 567–571.PubMedCrossRefGoogle Scholar
  5. 5.
    Beaulieu EE (1993) RU486 - a decade on, today and tomorrow. In Clinical Applications of Mifepristone RU486 and Other Antiprogestins. MS Donaldson, L Dorflinger, SS Brown, LZ Benet (eds). Washington, DC: National Academy Press, pp 71–119.Google Scholar
  6. 6.
    Philibert D (1985) Pharmacological profile of RU 486 in animals. In The Antiprogestin Steroid RU 486 in Human Fertility Control. EE Baulieu, SJ Segall (eds). New York: Plenum Press, pp 49–68.Google Scholar
  7. 7.
    Klijn JGM, de Jong FH, Bakker GH, Lamberts SWJ, Rodenburg CJ, Aliexa-Figusch J (1989) Antiprogestins, a new form of endocrine therapy for human breast cancer. Cancer Res 49: 2851–2856.PubMedGoogle Scholar
  8. 8.
    Ulmann A, Silvestre L, Chemama L, Rezvani Y, Renault M, Aguillaume J, Baulieu EE (1992) Medical termination of early pregnancy with RU486 (mifepristone) followed by a prostaglandin analogue: Study in 16,369 women. Scand J Obstet Gynecol 71: 278–283.CrossRefGoogle Scholar
  9. 9.
    Teutsch G, Belanger A (1979) Regional and stereospecific synthesis of 11ß-substituted 19-nor-steroids. Tetrahedron Lett V17: 2051–2054.CrossRefGoogle Scholar
  10. 10.
    Bigsby RM, Young PCM (1992) Estrogen-like effects of the antiprogestin ZK 98.299. In Proceedings of the 74th Annual Meeting of the Endocrine Society, San Antonio, Texas, June 24–27, 1992. San Antonio, Endocrine Society, p 233.Google Scholar
  11. 11.
    Gronemeyer H, Benhamou B, Berry M, Bocquel MT, Gofflo D, Garcia T, Leronge T, Metzger D, Meyer ME, Tora L, Vergezac A, Chambon D (1992) Mechanism of antihormone action. J Steroid Biochem Mol Biol 41: 217–221.PubMedCrossRefGoogle Scholar
  12. 12.
    Takimoto GS, Tasset DM, Eppert AC, Horwitz KB (1992) Hormone-induced progesterone receptor phosphorylation consists of sequential DNA-independent and DNA-dependent stages: Analysis with zinc finger mutants and the progesterone antagonist ZK 98299. Proc Natl Acad Sci USA 98: 3050–3054.CrossRefGoogle Scholar
  13. 13.
    Delabre K, Guiochon-Mantel A, Milgrom E (1993) In vivo evidence against the existence of antiprogestins disrupting receptor binding to DNA. Proc Natl Acad Sci USA 90: 4421–425.PubMedCrossRefGoogle Scholar
  14. 14.
    Horwitz KB, Takimoto GS, Tung L (1994) When steroid antagonists act like agonists: Issues of hormone resistance and tissue specificity. In Program and abstracts, Dallas, IX International Congress on Hormonal Steroids, September 1994, Dallas, Texas.Google Scholar
  15. 15.
    Bardon S, Vignon F, Chalbos D, Rochefort H (1985) RU 486, a progestin and glucocorticoid antagonist, inhibits the growth of breast cancer cells via progesterone receptor. J Clin Endocrinol Metab 60: 692.PubMedCrossRefGoogle Scholar
  16. 16.
    Horwitz KB (1985) The antiprogestin RU 38486: Receptor mediated progestin versus antiprogestin actions screened in estrogen-sensitive T 47 D10 human breast cancer cells. Endocrinology 116: 2236–2245.PubMedCrossRefGoogle Scholar
  17. 17.
    Bardon S, Vignon F, Montcourrier P, Rochefort H (1987) Steroid receptor-mediated cytotoxity of an antiestrogen and an antiprogestin in breast cancer cells. Cancer Res 47: 1441–1448.PubMedGoogle Scholar
  18. 18.
    Gill P, Vignon F, Bardon S, Derocq S, Rochefort H (1987) Difference between R 5020 and the antiprogestin RU 486 on anti-proliferative effects on human breast cancer cells. Breast Cancer Res Treat 10: 37–45.PubMedCrossRefGoogle Scholar
  19. 19.
    Terakawa N, Shimizu I, Tanizawa O, Matsumoto K (1988) RU 486, a progestin antagonist, binds to progesterone receptors in a human endometrial cancer cell line and reverses the growth inhibition by progestins. J Steroid Biochem 31: 161–166.PubMedCrossRefGoogle Scholar
  20. 20.
    Van den Berg HW, Martin JHJ, Lynch M (1990) Progestin/anti-progestin action towards human breast cancer cell lines differing in their progesterone receptor content. Br J Pharmacol 101(Suppl).Google Scholar
  21. 21.
    Thomas M, Monet JD (1992) Combined effects of RU 486 and Tamoxifen on the growth and cell cycle phases of the MCF-7 cell line. J Clin Endocrinol Metab 75: 865–870.PubMedCrossRefGoogle Scholar
  22. 22.
    Classen S, Possinger K, Pelka-Fleischer R, Wilmanns W (1993) Effect of Onapristone and medroxy-progesterone acetate on the proliferation and hormone receptor concentration of human breast cancer cells. J Steroid Biochem Mol Biol 45: 315–319.PubMedCrossRefGoogle Scholar
  23. 23.
    Van den Berg HW, Lynch M, Martin JHJ (1993) The relationship between affinity progestins and antiprogestins for the progesterone receptor in breast cancer cells (ZR-PR-LT) and ability to down-regulate the receptor: Modulation via the glucocorticoid receptor. Eur J Cancer 29A: 1771–1775.PubMedGoogle Scholar
  24. 24.
    Maass N, Eidmann H, Arps H, Jonat W (1994) Progesterone antagonist ZK 98.299 (Onapristone) inhibits growth of the estrogen receptor (ER) and progesterone receptor (PR) positive breast cancer cell line MCF-7. Tumordiagn Ther 15: 6–11.Google Scholar
  25. 25.
    Bowden TR, Hissom JR, Moore MR (1989) Growth stimulation of T47D human breast cancer cells by the antiprogestin RU 486. Endocrinology 124: 2642–2646.PubMedCrossRefGoogle Scholar
  26. 26.
    Jeng MH, Jordan VC (1992) Estrogenic actions of RU 486 in estrogen responsive human breast cancer MCF-7 cells. Proc Am Assoc Cancer Res 282, abstr 1684.Google Scholar
  27. 27.
    Jeng M-H, Langan-Fahey SM, Jordan VC (1993) Estrogenic actions of RU 486 in hormone-responsive MCF-7 human breast cancer cells. Endocrinology 132: 2622–2630.PubMedCrossRefGoogle Scholar
  28. 28.
    Meei-Huey J, Langan-Fahey SM, Jordan VC (1993) Estrogenic actions of RU 486 in hormone responsive MCF-7 human breast cancer cells. Endocrinology 132: 2622–2630.CrossRefGoogle Scholar
  29. 29.
    Herman M, Bhakta A, Underwood B, Kodali S, Moudgil VK (1993) Interaction of progesterone receptor from T47D human breast cancer cells with different progestins and antiprogestins. Abstract book, Endocrine Society, Las Vegas, abstract 957, p 290.Google Scholar
  30. 30.
    Lu J, Matsumoto K, Nishizawa Y, Tanaka A, Hirose T, Sato B (1991) Nonclassical androgen actions of RU 38.486 in androgen-responsive Shionogi carcinoma 115 cells in serum-free culture. J Steroid Biochem Mol Biol 39: 329–335.PubMedCrossRefGoogle Scholar
  31. 31.
    Kloosterboer HJ, Deckers GHV, Van der Heuvel MJ, Loozen HJJ (1988) Screening of anti-progestagens by receptor studies and bioassays. J Steroid Biochem 31: 567–571.PubMedCrossRefGoogle Scholar
  32. 32.
    Mizutani T, Bhakta A, Kloosterboer HJ, Moudgil VK (1992) Novel anti-progestins Org 31806 and Org 31710 interaction with mammalian progesterone receptor and DNA binding of anti-steroid receptor complexes. J Steroid Mol Biol 42: 695–704.CrossRefGoogle Scholar
  33. 33.
    Michna H, Nishino Y, Schneider MR, Louton T, El Etreby MF (1991) A bioassay for the evaluation of antiproliferative potencies of progesterone antagonists. J Steroid Biochem Mol Biol 38: 359–365.PubMedCrossRefGoogle Scholar
  34. 34.
    Bargmann W, Fleischhauer K, Knopp A (1960) Über die Morphologie der Milchsekretion. II. Z Zellforsch 53: 545–568.Google Scholar
  35. 35.
    Bargmann W, Welsch W (1969) On the ultrastructure of the mammary gland. In Lactogenes. M Reynolds, SJ Folley (eds). Philadelphia: University of Pennsylvania Press, pp 43–52.Google Scholar
  36. 36.
    Haslam SZ, Shyalama G (1981) Relative distribution of estrogen and progesterone receptors among the epithelial, adipose, and connective tissue components of the normal mammary gland. Endocrinology 108: 825–830.PubMedCrossRefGoogle Scholar
  37. 37.
    Russo H, Russo JH (1987) Development of the human mammary gland. In The Mammary Gland. MC Neville, CW Daniel (eds). New York: Plenum, pp 53–68.Google Scholar
  38. 38.
    Haslam SZ (1988) Progesterone effects on deoxyribonucleic acid synthesis in normal mousse mammary glands. Endocrinology 122: 464–470.PubMedCrossRefGoogle Scholar
  39. 39.
    Russo IH, Medado J, Russo J (1989) Endocrine influences on the mammary glands. In Integument and Mammary Glands. TC Jones, U Mohr, RD Hunt (eds). Berlin: Springer Verlag, pp 252–266.Google Scholar
  40. 40.
    Neumann U, Mendoza A, Kühnel W, Nishino Y, Michna H (1996) A new assay for progestins. J Steroid Biochem Mol Biol, in press.Google Scholar
  41. 41.
    Michna H, Schneider MR, Nishino Y, El Etreby MF (1989) The antitumor mechanism of progesterone antagonists is a receptor mediated antiproliferative effect by induction of terminal cell death. J Steroid Biochem 34: 447–453.PubMedCrossRefGoogle Scholar
  42. 42.
    Schneider MR, Michna H, Nishino Y, El Etreby MF (1989) Antitumor activity of the progesterone antagonists ZK 98299 and RU486 in the hormone-dependent MXT mammary tumor model of the mouse and the DMBA- and MNU-induced mammary tumor model of the rat. Eur J Cancer Clin Oncol 25: 691–701.PubMedCrossRefGoogle Scholar
  43. 43.
    Michna H, Schneider MR, Nishino Y, El Etreby MF, McGuire WL (1990) Progesterone antagonists block the growth of experimental mammary tumors in G0V1 Breast Cancer Res Treat 17: 155–156.PubMedCrossRefGoogle Scholar
  44. 44.
    Bakker GH, Setyono-Han B, Portengen H, de Jong FH, Foekens JA, Klijn JGM (1990) Treatment of breast cancer with different antiprogestins: Preclinical and clinical studies. J Steroid Biochem Mol Biol 37: 789–794.PubMedCrossRefGoogle Scholar
  45. 45.
    Bakker GH, Setyono-Han B, de Jong FH, Klijn JGM (1987) Mifepristone in treatment of experimental breast cancer in rats. In Hormonal Manipulation of Cancer: Peptides, Growth Factors and New (Anti-) Steroidal Agents. JGM Klijn, R Paridaens, JA Foekens (eds). New York: Raven, pp 39–48.Google Scholar
  46. 46.
    Orlemans EOM, Deckers GH, Schoonen WGEJ, Kloosterboer HJ (1994) Pharmacology of the very selective antiprogestin Org 31710 and comparison with the antiprogesttins RU38486 and ZK 98299. Program and abstracts, Dallas TX, International Congress on Hormonal Steroids, p 81.Google Scholar
  47. 47.
    Michna H, Schneider MR, Nishino Y, El Etreby MF (1989) Antitumor activity of the antiprogesterones ZK 98.299 and RU 38.486 in hormone dependent rat and mouse mammary tumors: Mechanistic studies. Breast Cancer Res Treat 14: 275–288.PubMedCrossRefGoogle Scholar
  48. 48.
    Michna H, Nishino Y, Schneider MR (1993) Effective sequential treatment of experimental mammary carcinomas with Tamoxifen and the progesterone antagonist Onapristone. Proc Am Associ Cancer Res 34: 25.Google Scholar
  49. 49.
    Rumpel E, Michna H, Kühnel W (1993) Morphology of the rat uterus after long-term treatment with progesterone antagonists. Ann Anat 175: 141–149.PubMedGoogle Scholar
  50. 50.
    Michna H, Nishino Y, Hasan SH, Schneider MR (1993) Morphological and endocrine reactions of hormone dependent target organs to a progesterone receptor blockade by a progesterone antagonist. Ann Anat 175: 303.Google Scholar
  51. 51.
    Nishino Y, Michna H, Hasan SH, Schneider MR (1991) The progesterone antagonist Onapristone modulates estrogen-dependent functions in different target organs in rats and mice. Acta Endocrinol 124(Suppl 1): 160.Google Scholar
  52. 52.
    Nishino Y, Michna H, Hasan SH, Schneider MR (1992) Involvement of the adrenal gland in the prolactin rise induced in the femal rat to an antiprogestin, Onapristone./Steroid Biochem Mol Biol 41: 841–845.Google Scholar
  53. 53.
    Koering MJ, Healy DL, Hodgen GD (1986) Morphologic response of endometrium to a progesterone receptor antagonist, RU 486, in monkeys. Fertil Steril 45: 280–287.PubMedGoogle Scholar
  54. 54.
    Wolf JP, Hsiu JG, Anderson TL, Ulman A, Baulieu EE, Hodgen GD (1989) Noncompetitive antiestrogenic effect of RU 486 in blocking the estrogen-stimulated luteinizing hormone surge and the proliferative action of estradiol on endometrium in castrated monkeys. Fertil Steril 52: 1055–1060.PubMedGoogle Scholar
  55. 55.
    Bigsby RM, Young PCM (1994) Estrogenic effects of the antiprogestin Onapristone in the rodent uterus. Am J Obstet Gynecol 171: 188–194.PubMedGoogle Scholar
  56. 56.
    Tachi C, Tachi S, Lindner HR (1972) Modification by progesterone of oestradiol-induced cell proliferation, RNA synthesis and oestradiol distribution in the rat uterus. J Reprod Fertil 31: 59–76.PubMedCrossRefGoogle Scholar
  57. 57.
    Clark BF (1973) The effect of estrogen and progesterone on uterine cell division and epithelial morphology in spayed-hypophysectomized rats. J Endocrinol 56: 341–342.PubMedCrossRefGoogle Scholar
  58. 58.
    Martin L, Finn CA, Tinder G (1973) Hypertrophy and hyperplasia in the mouse uterus after oestrogen treatment: An autoradiographic study. J Endocrinol 56: 133–144.PubMedCrossRefGoogle Scholar
  59. 59.
    Bigsby RM, Cunha GR (1985) Effects of progestins and glucocorticoids on deoxyribonucleic acid synthesis in the uterus of the neonatal mouse. Endocrinology 117: 2520–2526.PubMedCrossRefGoogle Scholar
  60. 60.
    Van der Schoot P, Bakker GH, Klijn JGM (1987) Effects of the progesterone antagonist RU 486 (mifepristone) on ovarian activity in the rat. Endocrinology 121: 1375–1382.PubMedCrossRefGoogle Scholar
  61. 61.
    Bigsby RM, Cunha GR (1988) Progesterone and dexamethasone inhibition of uterine epithelial proliferation in two models of estrogen-independent growth. Am J Obstet Gynecol 518: 646–650.Google Scholar
  62. 62.
    Van der Schoot P, Uilenbroek JT, Slappendel EJ (1990) Effect of the progesterone antagonist mifepristone on the hypothalamo-hypophysial-ovarian axis in rats. J Endocrinol 124: 425–432.PubMedCrossRefGoogle Scholar
  63. 63.
    Jo T, Terada N, Saji F, Tanizawa O (1993) Inhibitory effects of estrogen, progesterone, androgen and glucocorticoid on death of neonatal mouse uterine epithelial cells induced to proliferate by estrogen. J Steroid Biochem Mol Biol 46: 25–32.PubMedCrossRefGoogle Scholar
  64. 64.
    Rauch M, Loosfeld H, Philibert D, Milgrom E (1985) Mechanism of action of an antiprogesterone, RU 468, in the rabbit endometrium. Effects of RU 468 on the progesterone receptor and on the expression of the uteroglobin gene. Eur J Biochem 148: 213–18.PubMedCrossRefGoogle Scholar
  65. 65.
    Van Uem JFHM, Hsiu JG, Chillik CF (1989) Contraceptive potential of RU 486 by ovulation inhibition. I. Pituitary versus ovarian action with blockade of estrogen-induced endometrial proliferation. Contraception 40: 171–184.PubMedCrossRefGoogle Scholar
  66. 66.
    Neulen J, Williams RF, Hodgen GD (1990) RU 486: Induction of dose dependent elevations of estradiol receptor in endometrium from ovariectomized monkeys. J Clin Endocrinol Metab 71: 1074–1075.PubMedCrossRefGoogle Scholar
  67. 67.
    Chwalisz K, Hegele-Hartung C, Fritzemeier KH, Beier HM, Elger W (1991) Inhibition of the estradiol-mediated endometrial gland formation by the antigestagen Onapristone in rabbits: Relationship to uterine estrogen receptors. Endocrinology 129: 312–322.PubMedCrossRefGoogle Scholar
  68. 68.
    Slayden OD, Brenner RM (1994) RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys (Macaca mulatto). J Clin Endocrinol Metab 78: 440–448.PubMedCrossRefGoogle Scholar
  69. 69.
    Slayden OD, Hirst JJ, Brenner RM (1993) Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment. Endocrinology 132: 1845–1856.PubMedCrossRefGoogle Scholar
  70. 70.
    Gottardis MM, Jordan VC (1988) Development of tamoxlfen-stimulated growth of MCF-7 tumors in athymic mice after long-term antiestrogen administration. Cancer Res 48: 5183–5187.PubMedGoogle Scholar
  71. 71.
    Reddel RR, Sutherland RL (1984) Tamoxifen stimulation of human breast cancer proliferation in vitro: A possible model for tamoxifen tumour flare. Eur J Cancer Clin Oncol 20: 1419–1424.PubMedCrossRefGoogle Scholar
  72. 72.
    Martin L (1981) Effects of antiestrogens on cell proferation in the rodent reproductive tract. In Non-steroidal Antioestrogens. Molecular Pharmacology and Antitumor Activity. RL Sutherland, VC Jordan (eds). New York: Academic Press, pp 47–55.Google Scholar
  73. 73.
    Howell A, Dodwell D, Laidlaw J, Anderson H, Anderson E (1990) Tamoxifen as an agonist for metastatic breast cancer. In Endocrine Therapy of Breast Cancer IV. A Goldhirsch (eds). Berlin: Springer Verlag, pp 49–58.Google Scholar
  74. 74.
    Osborne C (1993) Mechanisms for tamoxifen resistance in breast cancer: Possible role of tamoxifen metabolism. J Steroid Biochem Mol Biol 47: 83–90.PubMedCrossRefGoogle Scholar
  75. 75.
    Lahti E, Blanco G, Kauppila A, Apaja-Sarkkinen M, Taskinen P, Laatikainen T (1993) Endometrial changes in postmenopausal breast cancer patients receiving tamoxifen. Obstet Gynecol 81: 660–664.PubMedGoogle Scholar
  76. 76.
    Wakeling AE, Bowler J (1987) Steroidal pure antiestrogens. J Endocrinol 112: R7–10.PubMedCrossRefGoogle Scholar
  77. 77.
    Brunne N, Bronzert D, Vindelov L, Rygaard K, Spang-Thomsen M, Lippman ME (1989) Effect on growth and cell cycle kinetics of estradiol and tamoxifen on MCF-7 human breast cancer cells grown in vitro and in nude mice. Cancer Res 49: 1515–1520.PubMedGoogle Scholar
  78. 78.
    Lamberts SWJ, Koper JW, de Jong FH (1991) The endocrine effects of long-term treatment with mifepristone (RU 486). J Clin Endocrinol Metab 73: 187–191.PubMedCrossRefGoogle Scholar
  79. 79.
    Jordan VC (1992) The role of tamoxifen in the treatment and prevention of breast cancer. Curr Probl Cancer 16: 134–176.CrossRefGoogle Scholar
  80. 80.
    Wakeling AE, Bowler J (1988) Biology and mode of action of pure antiestrogens. J Steroid Biochem 30: 141–149.PubMedCrossRefGoogle Scholar
  81. 81.
    Stöckemann K, Chwalisz K (1993) Effects of the new progesterone antagonist ZK 136799 on surgically-induced endometriosis. Program of the 40th Annual Meeting of Obstetrics, Toronto, abstract.Google Scholar
  82. 82.
    Stöckemann K, Chwalisz K (1993) Effects of the progesterone antagonist Onapristone and ZK 136799 on surgically-induced endometriosis in rats. Program of the 37th Symposium of the German Endocrine Society Berlin, abstract.Google Scholar
  83. 83.
    Kettel LM, Murphy AA, Mortola JF, Liu JH, Ulmann A, Yen SS (1991) Endocrine responses to long-term administration of the antiprogesterone RU 486 in patients with pelvic endometriosis. Fertil Steril 56: 402–407.PubMedGoogle Scholar
  84. 84.
    Murphy AA, Kettel LM, Morales AJ, Roberts VJ, Yen SS (1993) Regression of uterine leiomyomata in response to the antiprogesterone RU486. J Clin Endocrinol Metab 76: 513–517.PubMedCrossRefGoogle Scholar
  85. 85.
    McDonnell DP, Goldman ME (1994) RU 486 exerts antiestrogenic activities through a novel progesterone receptor A-form mediated mechanism. J Biol Chem 269: 1945–1949.Google Scholar
  86. 86.
    Tora A, Mullick A, Metzger D, Ponglikitmongkol M, Park I, Chambon P (1989) The cloned human oestrogen receptor contains a mutation which alters its hormone binding properties. EMBO J 49: 1981–1986.Google Scholar
  87. 87.
    Klein-Hitpass L, Schorpp M, Wagner U, Ryffel GU (1986) An estrogen-responsive element derived from the 5’ flanking region of the Xenopus vitellogenin A2 gene functions in trans-fected human cells. Cell 46: 1053–1061.PubMedCrossRefGoogle Scholar
  88. 88.
    Döhler KD, Wuttke W (1975) Changes with age in levels of serum gonadotropins, prolactin, and gonadal steroids in prepubertal male and female rats. Acta Endocrinol 97: 898–916.Google Scholar
  89. 89.
    Horwitz KB, McGuire WL (1977) Progesterone and progesterone receptors in experimental breast cancer. Cancer Res 37: 1733–1738.PubMedGoogle Scholar
  90. 90.
    Vollmer G, Michna H, Ebert K, Knuppen R (1992) Downregulation of tenascin expression by antiprogestins during terminal differentiation of rat mammary tumors. Cancer Res 52: 4642–4648.PubMedGoogle Scholar
  91. 91.
    Gehring S, Michna H, Kühnel W, Nishino Y, Schneider MR (1991) Morphometrical and histochemical studies on the differentiation potential of progesterone antagonists in experimental mammary carcinomas. Acta Endocrinol 124: 177.Google Scholar
  92. 92.
    Tenniswood M, Michna H (1995) Apoptosis in Hormone-Dependent Cancers. Berlin: Springer Verlag.Google Scholar
  93. 93.
    Knabbe C, Lippmann ME, Flanders KC, Kasid A, Derynyck R, Dickson RB (1987) Evidence that transforming growth factor-beta is a hormonally regulated negative growth factor in human breast cancer cells. Cell 48: 417–428.CrossRefGoogle Scholar
  94. 94.
    Bursch W, Grasl-Kraupp B, Ellinger A, Török L, Kienzl H, Miillauer L, Schufte-Hermann R (1995) Active cell death and cancer. In M Tenniswood, H Michna (eds). Apoptosis in Hormone Dependent Cancers. Berlin: Springer Verlag, pp 83–103.Google Scholar
  95. 95.
    Colletta AA, Wakefield LM, Howell FV, van Roozendaal KE, Danielpour D, Ebbs SR, Sporn MB, Baum M (1992) Anti-estrogens induce the secretion of active transforming growth factor-beta from fetal fibroblasts. Br J Cancer 62: 405–409.Google Scholar
  96. 96.
    Scott RE, Hoerl BJ, Wille JJ, Florine DL, Krawisz BR, Kankatsu Y (1982) Coupling of proadipocyte growth arrest and differentiation. IL A cell cycle model for the physiological control of cell proliferation. J Cell Biol 94: 400–405.PubMedCrossRefGoogle Scholar
  97. 97.
    Wille JJ, Maercklein PB, Scott RE (1982) Neoplastic transformation and defective control of cell proliferation and differentiation. Cancer Res 42: 5139–5146.PubMedGoogle Scholar
  98. 98.
    Clark GM, Dressler LG, Owens MA, Pounds G, Oldaker T, McGuire WL (1989) Prediction of relapse or survival in patients with node-negative breast cancer by DNA flow cytometry. N Engl J Med 320: 627–633.PubMedCrossRefGoogle Scholar
  99. 99.
    McGuire WL, Dressler LG (1985) Emerging impact of flow cytometry in predicting recurrence and survival in breast cancer patients. J Natl Cancer Inst 75: 405–410.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1996

Authors and Affiliations

  • H. Michna
  • K.-H. Fritzemeier
  • K. Parczyk
  • Y. Nishino
  • M. R. Schneider

There are no affiliations available

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