Progesterone receptor antagonists (antiprogestins)

Drugs of the Future

Volumn 27, Issue 11, 2002, Pages 1113-1123

  Hess Stumpp, Holger ^a   Hoffmann, Jens ^a   Fuhrmann, Ulrike ^a  

^a BAYER PHARMA AG   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

11BETA (4 ACETYLPHENYL) 17BETA HYDROXY 17ALPHA (1,1,2,2,2 PENTAFLUOROETHYL)ESTRA 4,9 DIEN 3 ONE; ANTIGESTAGEN; MIFEPRISTONE; NITRIC OXIDE; NITRIC OXIDE SYNTHASE INHIBITOR; ONAPRISTONE; PROGESTERONE; PROGESTERONE RECEPTOR; UNCLASSIFIED DRUG; ZK 137316;

ANIMAL MODEL; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; BIRTH CONTROL; BREAST CANCER; CANCER THERAPY; CHEMICAL MODIFICATION; CONTRACEPTION; DECIDUALIZATION; DNA BINDING; DRUG EFFICACY; DRUG STRUCTURE; DRUG SYNTHESIS; ENDOMETRIOSIS; ENDOMETRIUM; HORMONAL THERAPY; MALIGNANT TRANSFORMATION; METRORRHAGIA; MOLECULAR DYNAMICS; MOLECULAR MECHANICS; MOLECULAR MODEL; OVULATION INHIBITION; PRIMATE; RECEPTOR BLOCKING; REVIEW;

EID: 0036879150     PISSN: 03778282     EISSN: None     Source Type: Journal    
DOI: 10.1358/dof.2002.027.11.857029     Document Type: Review

References (118)

1. Espey, L.L., Lipner, H. Ovulation. In: The Physiology of Reproduction, Vol. 1. E. Knobil, J.D. Neill (Eds.). Raven Press: New York 1994, 725-80.
2. Niswender, G.D., Nett, T.M. The corpus luteum and its control in infraprimate species. In: The Physiology of Reproduction, Vol. 1. E. Knobil, J.D. Neill (Eds.). Raven Press: New York 1994, 781-816.
3. Beier, H.M., Mootz, U., Hegele-Hartung, C. Studies on the establishment of mammalian pregnancy: Synchronization of the maternal and the embryonic systems. In: Reproductive Biology and Medicine. A.F. Holstein, K.D. Voigt, D. Grässlin (Eds.). Diesbach Verlag: Berlin 1989, 210-23.
4. Csapo, A.I. The "seesaw" theory of regulatory mechanisms of pregnancy. Am J Obstet Gynecol 1975, 121: 578-81.
5. Chwalisz, K., Garfield, R.E. Antiprogestins in the induction of labor. Ann NY Acad Sci 1994, 734: 387-413.
6. Conneely, O.M., Mulac-Jericevic, B., Lydon, J.P., De Mayo, F.J. Reproductive functions of the progesterone receptor isoforms: Lessons from the knock-out mice. Mol Cell Endocrinol 2001, 179: 97-103.
7. Green, S., Chambon, P. Nuclear receptors enhance our understanding of transcription regulation. Trends Genet 1988, 4: 309-14.
8. Beato, M., Sanchez-Pacheco, A. Interaction of steroid hormone receptors with the transcription initiation complex. Endocrine Rev 1996, 17: 587-609.
9. Robyr, D., Wolffe, A.P., Wahli, W. Nuclear hormone receptor coregulators in action: Diversity for shared tasks. Mol Endocrinol 2000, 14: 329-47.
10. Liu, J.H., Garzo, G., Morris, S., Stuenkel, C.A., Ulmann, A., Yen, S.S.C. Disruption of follicular maturation and delay of ovulation after administration of the antiprogesterone RU 486. J Clin Endocrinol Metab 1987, 65: 1135-40.
11. Shoupe, D., Mishell, D.J., Page, M.A., Madkour, H., Spitz, I.M., Lobo, R.A. Effects of the antiprogesterone RU 486 in normal women. II. Administration in the late follicular phase. Am J Obstet Gynecol 1987, 157: 1421-6.
12. Luukkainen, T., Heikinheimo, O. Inhibition of folliculogenesis and ovulation by the antiprogesterone RU 486. Fertil Steril 1988, 49: 961-3.
13. Donath, J., Michna, H., Nishino, Y. The antiovulatory effect of the antiprogestin onapristone could be related to down-regulation of intra-ovarian progesterone (receptors). J Steroid Biochem Mol Biol 1997, 62: 107-18.
14. Croxatto, H.B., Kovács, L., Massai, R. et al. Effects of long-term low-dose mifepristone on reproductive function in women. Hum Reprod 1998, 13: 793-8.
15. Zelinski-Wooten, M.B., Slayden, O.D., Chwalisz, K., Hess, D.L, Brenner, R.M., Stouffer, R.L. Chronic treatment of female rhesus monkeys with low doses of the antiprogestin ZK 137316: Establishment of a regimen that permits normal menstrual cyclicity. Hum Reprod 1998, 13: 259-67.
16. Elger, W., Bartley, J., Schneider, B., Kaufmann, G., Schubert, G., Chwalisz, K. Endocrine pharmacological characterization of progesterone antagonists and progesterone receptor modulators with respect to PR-agonistic and antagonistic activity. Steroids 2000, 65: 713-23.
17. Chwalisz, K. The use of progesterone antagonists for cervical ripening and as adjunct to labour and delivery. Hum Reprod 1994, 9(Suppl. 1): 131-61.
18. Brenner, R.M., Slayden, O.D. Oestrogen action in the endometrium and oviduct of rhesus monkeys during RU 486 treatment. Hum Reprod 1994, 9(Suppl. 1): 82-97.
19. Slayden, O.D., Zelinski-Wooten, M.B., Chwalisz, K., Stouffer, R.L., Brenner, R.M. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137316: Morphometric assessment of the uterus and oviduct. Hum Reprod 1998, 13: 269-77.
20. Chwalisz, K., Brenner, R.M., Fuhrmann, U., Hess-Stumpp, H., Elger, W. Antiproliferative effects of progesterone antagonists and progesterone receptor modulators on the endometrium. Steroids 2000, 65: 741-51.
21. Horwitz, K.B. Antiprogestins and the treatment of breast cancer. In: Clinical Applications of Mifepristone (RU 486) and Other Antiprogestins. M.S. Donaldson, L. Dorflinger, S.S. Brown, L.Z. Benet (Eds.). National Academy Press: Washington DC 1993, 210-28.
22. Klijn, J.G.M., Setyono-Han, B., Sander, H.J. et al. Pre-clinical and clinical treatment of breast cancer with antiprogestins. Hum Reprod 1994, 9(Suppl. 1): 181-9.
23. Robertson, J.F., Willsher, P.C., Winterbottom, L., Blamey, R.W., Thorpe, S. Onapristone, a progesterone receptor antagonist, as first line therapy in primary breast cancer. Eur J Cancer 1999, 35: 214-8.
24. Klijn, J.G.M., Setyono-Han, B., Foekens, J.A. Progesterone antagonists and progesterone receptor modulators in the treatment of breast cancer. Steroids 2000, 65: 825-30.
25. Fuhrmann, U., Hess-Stumpp, H., Cleve, A. et al. Synthesis and biological activity of a novel highly potent progesterone receptor antagonist. J Med Chem 2000, 43: 5010-6.
26. Philibert, D., Deraedt, R., Teutsch, G. RU 486: A potent antiglucocorticoid in vivo. 8th Int Cong Pharmacol (Toronto), 1981, Abst 1463.
27. Belanger, A., Philibert, D., Teutsch, G. Regio- and stereo-specific synthesis of 11β-substituted 19-norsteroids. Steroids 1981, 37: 361-82.
28. Herrmann, W., Wyss, R., Riondel, A. et al. The effects of an antiprogesterone steroid in women: Interruption of the menstrual cycle and of early pregnancy. CR Acad Sci 1982, 204: 933-8.
29. Klein-Hitpass, L., Cato, A.C., Henderson, D., Ryffel G.U. Two types of antiprogestins identified by their differential action in transcriptionally active extracts from T47D cells. Nucl Acid Res 1991, 19: 1227-34.
30. Wiechert, R., Neef, G. Synthesis of antiprogestational steroids. J Steroid Biochem 1987, 27: 851-8.
31. Cleve, A., Neef, G., Ottow, E., Scholz, S., Schwede, W. Synthesis of 14β-H antiprogestins. Tetrahedron 1995, 51: 5563-72.
32. Ottow, E., Neef, G., Wiechert, R. Stereo- and regiospecific 6-endo-trig-cyclization of aryl radicals, an entry to novel progesterone antagonists of the androstane series. Angew Chem Int Ed Engl 1989, 28: 773-6.
33. Cleve, A., Fritzemeier, K.H., Heinrich, N. et al. 11β-Aryl steroids in the androstene series. The role of the 11β-region in steroid progesterone receptor interaction. Tetrahedron 1996, 52: 1529-42.
34. Neef, G., Cleve, A., Ottow, E., Seeger, A., Wiechert, R. New steroids by Simmons-Smith methylenation and subsequent rearrangement. J Org Chem 1987, 52: 4143-6.
35. Kloosterboer, H.J., Deckers, G.H., de Gooyer, M.E., Dijkema, R., Orlemans, E.O.M., Schoonen, G.E.J. Pharmacological properties of a new selective antiprogestagen: Org 33628. Ann NY Acad Sci 1995, 761: 192-201.
36. Kastner, P., Krust, A., Turcotte, B. et al. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. EMBO J 1990, 9: 1603-14.
37. Conneely, O.M., Maxwell, B.L., Toft, D.O., Schrader, W.T., O'Malley, B.W. The A and B forms of the chicken progesterone receptor arise by alternate initiation of translation of a unique mRNA. Biochem Biophys Res Commun 1987, 149: 493-501.
38. Allan, G.F., Tsai, S.Y., Tsai, M.-J., O'Malley, B.W. Ligand-dependent conformational changes in the progesterone receptor are necessary for events that follow DNA binding. Proc Natl Acad Sci USA 1992, 89: 11750-4.
39. Vegeto, E., Allan, G.F., Schrader, W.T., Tsai, M.-J., McDonnell, D.P., O'Malley, B.W. The mechanism of RU486 antagonism is dependent on the conformation of the carboxy-terminal tail of the human progesterone receptor. Cell 1992, 69: 703-13.
40. Weigel, N.L., Beck, C.A., Estes, P.A. et al. Ligands induce conformational changes in the carboxyl- terminus of progesterone receptors which are detected by a site-directed antipeptide monoclonal antibody. Mol Endocrinol 1992, 6: 1585-97.
41. Clemm, D.L., Macy, B.L., Santiso-Mere, D., McDonnell, D.P. Definition of the critical cellular components which distinguish between hormone and antihormone activated progesterone receptor. J Steroid Biochem Mol Biol 1995, 53: 487-95,
42. Benhamou, B., Garcia, T., Lerouge, T. et al. A single amino acid that determines the sensitivity of progesterone receptors to RU486. Science 1992, 255: 206-9.
43. Wagner, B.L., Pollio, G., Leonhardt, S. et al. 16α-Substituted analogs of the antiprogestin RU486 induce a unique conformation in the human progesterone receptor resulting in mixed agonist activity. Proc Natl Acad Sci USA 1996, 93: 8739-44.
44. Bocquel, M.T., Ji, J., Ylikomi, T. et al. Type II antagonists impair the DNA binding of steroid hormone receptors without affecting dimerization. J Steroid Biochem Mol Biol 1993, 45: 205-15.
45. Edwards, D.P., Altmann, M., DeMarzo, A., Zhang, Y., Weigel, N.L., Beck, C.A. Progesterone receptor and the mechanism of action of progesterone antagonists. J Steroid Biochem Mol Biol 1995, 53: 449-58.
46. Neef, G., Beier, S., Elger, W., Henderson, D., Wiechert, R. New steroids with antiprogestational and antiglucocorticoid activities. Steroids 1994, 44: 349-72.
47. Vassen, L., Klotzbücher, M., Ulber, V., Ryffel, G.U., Klein-Hitpass, L. Regulation of progesterone receptor activity in cell culture systems and cell-free transcription. In: Cell Culture in Pharmaceutical Research. Proceedings of the Schering Research Foundation, Vol. 11. N.E. Fusenig, H. Graf (Eds.). Springer Verlag: Berlin 1994, 267-97.
48. Chwalisz, K., Stöckemann, K., Fuhrmann, U., Fritzemeier, K.H., Einspanier, A., Garfield, R.E. Mechanism of action of antiprogestins in the pregnant uterus. Ann NY Acad Sci 1995 761: 202-23.
49. El-Ashry, D., Onate, S.A., Nordeen, S.K., Edwards, D.P. Human progesterone receptor complexed with the antagonist RU 486 binds to hormone response elements in a structurally altered form. Mol Endocrinol 1990, 3: 1545-58.
50. Beck, C.A., Weigel, N.L., Moyer, M.L., Nordeen, S.K., Edwards, D.P. The progesterone antagonist RU486 acquires agonist activity upon stimulation of cAMP signaling pathways. Proc Natl Acad Sci USA 1992, 90: 4441-5.
51. Sartorius, C.A., Tung, L., Takimoto, G.S., Horwitz, K.B. Antagonist-occupied human progesterone receptors bound to DNA are functionally switched to transcriptional agonists by cAMP J Biol Chem 1993, 268: 9262-6.
52. Sartorius, C.A., Groshong, S.D., Miller, L.A. et al. New T47D breast cancer cell lines for the independent study of progesterone B- and A-receptors: Only antiprogestin-occupied B-receptors are switched to transcriptional agonists by cAMP. Cancer Res 1994, 54: 3868-77.
53. Selye, H., McGill, F.R.S. General pharmacology of the ovarian hormones. In: Textbook of Endocrinology. H. Selye (Ed.). University of Montreal: Montreal 1947, Acta Endocrinologica, 347.
54. Ishwad, P.C., Katkam, R.R., Hinduja, I.N, Chwalisz, K., Elger, W., Puri, C.P. Treatment with a progesterone antagonist ZK 98.299 delays endometrial development without blocking ovulation in bonnet monkeys. Contraception 1993, 48: 57-69.
55. Beier, H.M., Hegele-Hartung, C., Mootz, U., Beier-Hellwig, K. Modification of endometrial cell biology using progesterone antagonists to manipulate the implantation window. Hum Reprod 1994, 9(Suppl. 1): 98-115.
56. Katkam, R.R., Gopalkrishnan, K., Chwalisz, K., Schillinger, E., Puri, C. P. Onapristone (ZK 98.299): A potential antiprogestin for endometrial contraception. Am J Obstet Gynecol 1995, 173: 779-87.
57. Hess-Stumpp, H., Fuhrmann, U., Cleve, A. et al. New approaches for contraception and treatment of gynecological disorders. In: Cell and Molecular Biology of Endometrium in Health and Disease. T. Maruo, D. Barlow, H. Mardon, S. Kennedy (Eds.). Soeisha: Osaka 2002, 55-77.
58. Herrmann, W.L., Schindler, A.M., Wyss, R., Bischof P. Effects of the antiprogesterone RU 486 in early pregnancy and during the menstrual cycle. In: The Antiprogestin Steroid RU 486 and Human Fertility Control. E.E. Baulieu, S.J. Segal (Eds.). Plenum Press: New York 1985, 179-98.
59. Hodgen, G.D. Antiprogestins: The political chemistry of RU 486. Fertil Steril 1991, 56: 394-5.
60. Bartley, J., Brown, A., Elton, R., Baird, D.T. Double-blind randomized trial of mifepristone in combination with vaginal gemeprost or misopristol for induction of abortion up to 63 days gestation. Hum Reprod 2001, 16: 2098-102.
61. Tang, O.S., Thong, K.J., Baird, D.T. Second trimester medical abortion with mifepristone and gemeprost: A review of 956 cases. Contraception 2001, 64: 29-32.
62. Brown, A., Cheng, L., Lin, S., Baird, D.T. Daily low-dose mifepristone has contraceptive potential by suppressing ovulation and menstruation: A double-blind randomized control trial of 2 and 5 mg per day for 120 days. J Clin Endocrinol Metab 2002, 87: 63-70.
63. Baird, D.T. Clinical uses of antiprogestogens. J Soc Gynecol Invest 2000, 7: S49-52.
64. Kloosterboer, H.J., Deckers, G.H., Schoonen, W.G.E.J. et al. Preclinical experience with two selective progesterone receptor modulators on breast and endometrium. Steroids 2000, 65: 733-40.
65. Parr, M.B., Parr, E.L. The implantation reaction. In: Biology of the Uterus, 2nd Ed. R.M. Wynn, W.P. Jolie (Eds.). Plenum Press: New York 1989, 233-67.
66. Loke Y.W., King, A. (Eds.). Human Implantation. Cell Biology and Immunology. Cambridge University Press: Cambridge 1995.
67. Rinkenberger, J.L., Cross, J.C., Werb, Z. Molecular genetics of implantation in the mouse. Dev Gen 1997, 21: 6-20.
68. Carson, D.D. (Ed.). Embryo Implantation. Molecular, Cellular and Clinical Aspects. Springer Verlag: New York 1999.
69. Lessey, B.A. The role of the endometrium during embryo implantation. Hum Reprod 2000, 15(Suppl. 6): 39-50.
70. Loke, Y.W., King, A. Immunology of implantation. Baillieres Best Pract Res Clin Obstet Gynaecol 2000, 14: 827-37.
71. Paria, B.C., Lim, H., Das, S.K., Reese, J., Dey, S.K. Molecular signaling in uterine receptivity for implantation. Semin Cell Dev Biol 2000, 11: 67-76.
72. Kennedy, T.G. Evidence for a role for prostaglandins in the initiation of blastocyst implantation in the rat. Biol Reprod 1977, 16: 289-91.
73. Evans, C.A., Kennedy, T.G. The importance of prostaglandin synthesis for the initiation of blastocyst implantation in the hamster. J Reprod Fertil 1978, 54: 255-61.
74. Kennedy, T.G. Timing of uterine sensitivity for the decidual cell reaction: Role of prostaglandins. Biol Reprod 1980, 22: 519-25.
75. Lim, H., Gupta, R.A., Ma, W.G. et al. Cyclo-oxygenase-2-derived prostacyclin mediates embryo implantation in the mouse via PPARdelta. Gen Dev 1999, 13: 1561-74.
76. Psychoyos, A., Nikas, G., Gravanis, A. The role of prostaglandins in blastocyst implantation. Hum Reprod 1995, 10(Suppl. 2): 30-42.
77. Nathan, C., Xie, Q.N. Nitric oxide synthases: Roles, tolls, and controls. Cell 1994, 78: 915-8.
78. Chwalisz, K., Buhimschi, I., Garfield, R.E. Role of nitric oxide in obstetrics. Prenat Neonat Med 1996, 1: 292-329.
79. Izumi, H., Yallampalli, C., Garfield, R.E. Gestational changes in L-arginine-induced relaxation of pregnant rat and human myometrial smooth muscle. Am J Obstet Gynecol 1993, 169: 1329-37.
80. Sladek, S.M., Regenstrin, A.C., Lykins, D., Roberts, J.M. NO synthase activity in pregnant rabbits uterus decreases on the last day of pregnancy. Am J Obstet Gynecol 1993, 169: 1285-91.
81. Buhimschi, I., Ali, M., Jain, V., Chwalisz, K., Garfield, R.E. Different regulation of nitric oxide in the uterus and cervix during pregnancy and labour. Hum Reprod 1996, 11: 1755-66.
82. Liao, Q.P., Buhimschi, I., Chwalisz, K., Garfield, R.E. Regulation of vascular adaptation during pregnancy and post-partum: Effects of nitric oxide inhibition and steroid hormones. Hum Reprod 1997, 12: 2777-84.
83. Purcell, T.L., Buhimschi, I., Given, R., Chwalisz, K., Garfield, R.E. Inducible nitric oxide synthase is present in the rat placenta at the fetal-maternal interface and decreases prior to labour. Mol Hum Reprod 1997, 3: 485-91.
84. Ali, M., Buhimschi, I., Chwalisz, K., Garfield, R.E. Changes in expression of nitric oxide synthase isoforms in rat uterus and cervix during pregnancy and parturition. Mol Hum Reprod 1997, 3: 995-1003.
85. Purcell, T.L., Given, R., Chwalisz, K., Garfield, R.E. Changes in expression of nitric oxide synthase distribution during implantation in the mouse. Mol Hum Reprod 1999, 5: 467-75.
86. Chwalisz, K., Winterhager, E., Thienel, T., Garfield, R.E. Synergistic role of nitric oxide and progesterone during the establishment of pregnancy in the rat. Hum Reprod 1999, 14: 542-52.
87. Pike, M.C., Ross, R.K. Progestins and menopause: Epidemiological studies of risk of endometrial and breast cancer. Steroids 2000, 65: 659-64.
88. Chwalisz, K., Stöckemann, K., Fritzemeier, K.H., Fuhrmann, U. Modulation of oestrogenic effects by progesterone antagonists in the rat uterus. Hum Reprod Update 1998, 4: 570-83.
89. Chwalisz, K. Role of progesterone in the control of labor. In: Basic Mechanisms Controlling Term and Preterm Birth, Ernst Schering Research Foundation Workshop 7. K. Chwalisz, R.E. Garfield (Eds.). Springer Verlag: Berlin/Heidelberg 1993, 97-162.
90. Hodgen, G.D., van Uem, J.F.H.M., Chillik, C.F. et al. Non-competitive anti-oestrogenic activity of progesterone antagonists in primate models. Hum Reprod 1994, 9(Suppl. 1): 77-81.
91. Wolf, J.P., Hsiu, J.G., Anderson, T.L., Ulmann, A., Baulieu, E.E., Hodgen, G.D. Noncompetitive anti-estrogenic 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 1989, 52: 1055-60.
92. Slayden, O.D., Zelinski-Wooten, M.B., Chwalisz, K., Stouffer, R.L., Brenner R.M. Chronic treatment of cycling rhesus monkeys with low doses of the antiprogestin ZK 137316: Morphometric assessment of the uterus and oviduct. Hum Reprod 1998, 13: 269-77.
93. Slayden, D., Hirst, J.J., Brenner, R.M. Estrogen action in the reproductive tract of rhesus monkeys during antiprogestin treatment. Endocrinology 1993, 132: 1845-56.
94. Slayden, O.D., Brenner, R.M. RU 486 action after estrogen priming in the endometrium and oviducts of rhesus monkeys. J Clin Endocrinol Metab 1994, 78: 440-8.
95. Bergqvist, I.A. Hormonal regulation of endometriosis and the rationales and effects of gonadotrophin-releasing hormone agonist treatment: A review. Hum Reprod 1995, 10: 446-52.
96. Kettel, L.M., Hummel, W.P. Modern medical management of endometriosis. Obstet Gynecol Clin North Am 1997, 24: 361-73.
97. Vercellini, P. Endometriosis: What a pain it is. Sem Reprod Endocrinol 1997, 15: 251-62.
98. Haney, A.F. Endometriosis-associated infertility. Reprod Med Rev 1997, 6: 145-61.
99. Cirkel, U. Medical treatment of symptomatic endometriosis. Hum Reprod 1996, 11 (Suppl. 3): 89-101.
100. Kettel, L.M., Murphy, A.A., Mortola, J.F., Liu, J.H., Ulmann, A., Yen, S.S.C. Endocrine responses to long-term administration of the antiprogesterone RU 486 in patients with pelvic endometriosis. Fertil Steril 1991, 56: 402-7.
101. Kettel, L.M., Murphy, A.A., Morales, A.J., Ulmann, A., Baulieu, E.E., Yen, S.S.C. Treatment of endometriosis with the antiprogesterone mifepristone (RU 486). Fertil Steril 1996, 65: 23-8.
102. Kettel, L.M., Murphy, A.A., Morales, A.J., Yen, S.S.C. Preliminary report on the treatment of endometriosis with low-dose mifepristone (RU 486). Am J Obstet Gynecol 1998, 178: 151-6.
103. Lydon, J.P., DeMayo, F.J., Funk, C.R. et al. Mice lacking progesterone receptor exhibit pleiotropic reproductive abnormalities. Gen Dev 1995, 15: 2266-78.
104. Lydon, J.P., DeMayo, F.J., Conneely, O.M., O'Malley, B.W. Reproductive phenotpes of the progesterone receptor null mutant mouse. J Steroid Biochem Mol Biol 1996, 56: 67-77.
105. Lydon, J.P., Ge, G., Kittrell, F.S., Medina, D., O'Malley, B.W. Murine mammary gland carcinogenesis is critically dependent on progesterone receptor function. Cancer Res 1999, 59: 4276-84.
106. Sarup, J.C., Rao, K.V.S., Fox, C.F. Decreased progesterone binding and attenuated progesterone action in cultured human breast carcinoma cells treated with epidermal growth factor. Cancer Res 1988, 48: 5071-8.
107. Murphy, L.C., Dotzlaw, H., Johnson Wong, M.S., Miller, T., Murphy, L.J. Mechanisms involved in the evolution of progestin resistance in human breast cancer cells. Cancer Res 1991, 51: 2051-7.
108. Kip1. Mol Endocrinology 1997, 11: 1593-607
109. Musgrove, E.A., Lee, C.S., Cornish, A.L., Swarbrick, A., Sutherland, R.L. Antiprogestin inhibition of cell cycle progression in T-47D breast cancer cells is accompanied by induction of the cyclin-dependent kinase inhibitor p21. Mol Endocrinol 1997, 11: 54-66.
110. Lange, C.A., Richer, J.K., Shen, T., Horwitz, K.B. Convergence of progesterone and epidermal growth factor signaling in breast cancer. J Biol Chem 1998, 273: 31308-16.
111. Richer, J.K., Lange, C.A., Manning, N.G., Owen, G., Powell, R., Horwitz, K.B. Convergence of progesterone with growth factor and cytokine signaling in breast cancer. J Biol Chem 1998, 273: 31317-26.
112. Michna, H., Gehring, S., Kuhnel, W., Nishino, Y., Schneider, M.R. The antitumor potency of progesterone antagonists is due to their differentiation potential. J Steroid Biochem Mol Biol 1992, 43: 203-10.
113. Michna, H., Nishino, Y., Neef, G., McGuire, W.L., Schneider, M.R. Progesterone antagonists: Tumor-inhibiting potential and mechanism of action. J Steroid Biochem Mol Biol 1992, 41: 339-48.
114. Bergers, E., Book, J.P., van Driest, P.J. et al. Prognostic implications of different cell cycle analysis models of flow cytometric DNA histograms of 1,301 breast cancer patients: Results from the Multicenter Morphometric Mammary Carcinoma Project (MMMCP). Int J Cancer 1997, 74: 260-9.
115. Robertson, J.F.R., Willsher, P.C., Winterbottom, L., Blamey, R.W., Thorpe, S. Onapristone, a progesterone receptor antagonist, as first-line therapy in primary breast cancer. Eur J Cancer 1999, 35: 214-8.
116. Culig, Z., Hoffmann, J., Erdel, M. et al. Switch from antagonist to agonist of the androgen receptor bicalutamide is associated with prostate tumour progression in a new model system. Br J Cancer 1999, 81: 242-51.
117. El Etreby, M.F., Liang, Y., Lewis, R.W. Induction of apoptosis by mifepristone and tamoxifen in human LNCaP prostate cancer cells in culture. Prostate 2000, 43: 31-42.
118. El Etreby, M.F., Liang, Y., Johnson, M.H., Lewis, R.W. Antitumor activity of mifepristone in the human LNCaP, LNCaP-C4, and LNCaP-C4-2 prostate cancer models in nude mice. Prostate 2000, 42: 99-106.