The antiprogestin Lonaprisan inhibits breast cancer cell proliferation by inducing p21 expression

Molecular and Cellular Endocrinology

Volumn 333, Issue 1, 2011, Pages 37-46

  Busia, L ^a,b   Faus, H ^a   Hoffmann, J ^a,c   Haendler, B ^a  

^a BAYER PHARMA AG   (Germany)

^b FREIE UNIVERSITÄT BERLIN   (Germany)

^c EPO GmbH   (Germany)

Author keywords

Cell cycle arrest; Lonaprisan; P21; Progesterone receptor; Sp1

Indexed keywords

LONAPRISAN; PROGESTERONE RECEPTOR; PROTEIN P21; TRANSCRIPTION FACTOR SP1;

ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; BREAST CANCER; CANCER CELL; CELL CYCLE ARREST; CELL CYCLE G0 PHASE; CELL CYCLE G1 PHASE; CELL PROLIFERATION; CHROMATIN IMMUNOPRECIPITATION; CONTROLLED STUDY; CYTOTOXICITY; DNA SYNTHESIS; DRUG ACTIVITY; GENE ACTIVATION; HUMAN; HUMAN CELL; MUTATIONAL ANALYSIS; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN MODIFICATION; PROTEIN PHOSPHORYLATION;

ANTINEOPLASTIC AGENTS; APOPTOSIS; BREAST NEOPLASMS; CELL AGING; CELL CYCLE; CELL LINE, TUMOR; CELL PROLIFERATION; CYCLIN-DEPENDENT KINASE INHIBITOR P21; ESTRENES; FEMALE; HUMANS; LIGANDS; MUTATION; PHOSPHORYLATION; PROGESTERONE; PROGESTINS; PROMOTER REGIONS, GENETIC; RECEPTORS, PROGESTERONE; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; RNA INTERFERENCE; SP1 TRANSCRIPTION FACTOR;

EID: 78651443638     PISSN: 03037207     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mce.2010.11.034     Document Type: Article

References (47)

1. Afhüppe W., Sommer A., Müller J., Schwede W., Fuhrmann U., Möller C. Global gene expression profiling of progesterone receptor modulators in T47D cells provides a new classification system. J. Steroid Biochem. Mol. Biol. 2009, 113:105-115.
2. Afhüppe W., Beekman J.M., Otto C., Korr D., Hoffmann J., Fuhrmann U., Möller C. In vitro characterization of ZK 230211-A type III progesterone receptor antagonist with enhanced antiproliferative properties. J. Steroid Biochem. Mol. Biol. 2010, 119:45-55.
3. Baulieu E.E. Contragestion by the progesterone antagonist RU 486: a novel approach to human fertility control. Contraception 1987, 36(Suppl):1-5.
4. Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003, 362:419-427.
5. Boonyaratanakornkit V., Scott M.P., Ribon V., Sherman L., Anderson S.M., Maller J.L., Miller W.T., Edwards D.P. Progesterone receptor contains a proline-rich motif that directly interacts with SH3 domains and activates c-Src family tyrosine kinases. Mol. Cell 2001, 8:269-280.
6. Chang B.D., Watanabe K., Broude E.V., Fang J., Poole J.C., Kalinichenko T.V., Roninson I.B. Effects of p21Waf1/Cip1/Sdi1 on cellular gene expression: implications for carcinogenesis, senescence, and age-related diseases. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:4291-4296.
7. Chou Y.C., Uehara N., Lowry J.R., Shyamala G. Mammary epithelial cells of PR-A transgenic mice exhibit distinct alterations in gene expression and growth potential associated with transformation. Carcinogenesis 2003, 24:403-409.
8. Collado M., Serrano M. The power and the promise of oncogene-induced senescence markers. Nat. Rev. Cancer 2006, 6:472-476.
9. Conneely O.M., Mulac-Jericevic B., Arnett-Mansfield R. Progesterone signaling in mammary gland development. Ernst Schering Found Symp. Proc. 2007, 45-54.
10. Daniel A.R., Lange C.A. Protein kinases mediate ligand-independent derepression of sumoylated progesterone receptors in breast cancer cells. Proc. Natl. Acad. Sci. U.S.A. 2009, 106:14287-14292.
11. Daniel A.R., Qiu M., Faivre E.J., Ostrander J.H., Skildum A., Lange C.A. Linkage of progestin and epidermal growth factor signaling: phosphorylation of progesterone receptors mediates transcriptional hypersensitivity and increased ligand-independent breast cancer cell growth. Steroids 2007, 72:188-201.
12. De Amicis F., Zupo S., Panno M.L., Malivindi R., Giordano F., Barone I., Mauro L., Fuqua S.A., Ando S. Progesterone receptor B recruits a repressor complex to a half-PRE site of the estrogen receptor alpha gene promoter. Mol. Endocrinol. 2009, 23:454-465.
13. DeManno D., Elger W., Garg R., Lee R., Schneider B., Hess-Stumpp H., Schubert G., Chwalisz K. Asoprisnil (J867): a selective progesterone receptor modulator for gynecological therapy. Steroids 2003, 68:1019-1032.
14. Faivre E.J., Lange C.A. Progesterone receptors upregulate Wnt-1 to induce epidermal growth factor receptor transactivation and c-Src-dependent sustained activation of Erk1/2 mitogen-activated protein kinase in breast cancer cells. Mol. Cell Biol. 2007, 27:466-480.
15. Faivre E.J., Daniel A.R., Hillard C.J., Lange C.A. Progesterone receptor rapid signaling mediates serine 345 phosphorylation and tethering to specificity protein 1 transcription factors. Mol. Endocrinol. 2008, 22:823-837.
16. Faus H., Haendler B. Post-translational modifications of steroid receptors. Biomed. Pharmacother. 2006, 60:520-528.
17. Fuhrmann U., Hess-Stumpp H., Cleve A., Neef G., Schwede W., Hoffmann J., Fritzemeier K.H., Chwalisz K. Synthesis and biological activity of a novel, highly potent progesterone receptor antagonist. J. Med. Chem. 2000, 43:5010-5016.
18. Gadducci A., Biglia N., Cosio S., Sismondi P., Genazzani A.R. Progestagen component in combined hormone replacement therapy in postmenopausal women and breast cancer risk: a debated clinical issue. Gynecol. Endocrinol. 2009, 25:807-815.
19. Giangrande P.H., McDonnell D.P. The A and B isoforms of the human progesterone receptor: two functionally different transcription factors encoded by a single gene. Recent Prog. Horm. Res. 1999, 54:291-313. discussion; 313-294.
20. Gizard F., Robillard R., Gross B., Barbier O., Revillion F., Peyrat J.P., Torpier G., Hum D.W., Staels B. TReP-132 is a novel progesterone receptor coactivator required for the inhibition of breast cancer cell growth and enhancement of differentiation by progesterone. Mol. Cell Biol. 2006, 26:7632-7644.
21. Groshong S.D., Owen G.I., Grimison B., Schauer I.E., Todd M.C., Langan T.A., Sclafani R.A., Lange C.A., Horwitz K.B. Biphasic regulation of breast cancer cell growth by progesterone: role of the cyclin-dependent kinase inhibitors, p21 and p27(Kip1). Mol. Endocrinol. 1997, 11:1593-1607.
22. Ismail P.M., Amato P., Soyal S.M., DeMayo F.J., Conneely O.M., O'Malley B.W., Lydon J.P. Progesterone involvement in breast development and tumorigenesis--as revealed by progesterone receptor " knockout" and " knockin" mouse models. Steroids 2003, 68:779-787.
23. Kariagina A., Aupperlee M.D., Haslam S.Z. Progesterone receptor isoform functions in normal breast development and breast cancer. Crit. Rev. Eukaryot. Gene Expr. 2008, 18:11-33.
24. Kastner P., Krust A., Turcotte B., Stropp U., Tora L., Gronemeyer H., Chambon P. Two distinct estrogen-regulated promoters generate transcripts encoding the two functionally different human progesterone receptor forms A and B. Embo J. 1990, 9:1603-1614.
25. Lange C.A. Integration of progesterone receptor action with rapid signaling events in breast cancer models. J. Steroid Biochem. Mol. Biol. 2008, 108:203-212.
26. Lange C.A., Yee D. Progesterone and breast cancer. Womens Health (Lond Engl) 2008, 4:151-162.
27. Lange C.A., Sartorius C.A., Abdel-Hafiz H., Spillman M.A., Horwitz K.B., Jacobsen B.M. Progesterone receptor action: translating studies in breast cancer models to clinical insights. Adv. Exp. Med. Biol. 2008, 630:94-111.
28. 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, 59:4276-4284.
29. Mandal S., Davie J.R. Estrogen regulated expression of the p21 Waf1/Cip1 gene in estrogen receptor positive human breast cancer cells. J. Cell Physiol. 2010, 224:28-32.
30. Moore M.R., Conover J.L., Franks K.M. Progestin effects on long-term growth, death, and Bcl-xL in breast cancer cells. Biochem. Biophys. Res. Commun. 2000, 277:650-654.
31. Mote P.A., Graham J.D., Clarke C.L. Progesterone receptor isoforms in normal and malignant breast. Ernst Schering Found Symp. Proc. 2007, 77-107.
32. Musgrove E.A., Hamilton J.A., Lee C.S., Sweeney K.J., Watts C.K., Sutherland R.L. Growth factor, steroid, and steroid antagonist regulation of cyclin gene expression associated with changes in T-47D human breast cancer cell cycle progression. Mol. Cell Biol. 1993, 13:3577-3587.
33. 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.
34. Owen G.I., Richer J.K., Tung L., Takimoto G., Horwitz K.B. Progesterone regulates transcription of the p21(WAF1) cyclin-dependent kinase inhibitor gene through Sp1 and CBP/p300. J. Biol. Chem. 1998, 273:10696-10701.
35. Poole A.J., Li Y., Kim Y., Lin S.C., Lee W.H., Lee E.Y. Prevention of Brca1-mediated mammary tumorigenesis in mice by a progesterone antagonist. Science 2006, 314:1467-1470.
36. Richer J.K., Jacobsen B.M., Manning N.G., Abel M.G., Wolf D.M., Horwitz K.B. Differential gene regulation by the two progesterone receptor isoforms in human breast cancer cells. J. Biol. Chem. 2002, 277:5209-5218.
37. Roemer S.C., Donham D.C., Sherman L., Pon V.H., Edwards D.P., Churchill M.E. Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements. Mol. Endocrinol. 2006, 20:3042-3052.
38. Rossouw J.E., Anderson G.L., Prentice R.L., LaCroix A.Z., Kooperberg C., Stefanick M.L., Jackson R.D., Beresford S.A., Howard B.V., Johnson K.C., et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial. JAMA 2002, 288:321-333.
39. Samalecos A., Gellersen B. Systematic expression analysis and antibody screening do not support the existence of naturally occurring progesterone receptor (PR)-C, PR-M, or other truncated PR isoforms. Endocrinology 2008, 149:5872-5887.
40. Sartorius C.A., Melville M.Y., Hovland A.R., Tung L., Takimoto G.S., Horwitz K.B. A third transactivation function (AF3) of human progesterone receptors located in the unique N-terminal segment of the B-isoform. Mol. Endocrinol. 1994, 8:1347-1360.
41. Scarpin K.M., Graham J.D., Mote P.A., Clarke C.L. Progesterone action in human tissues: regulation by progesterone receptor (PR) isoform expression, nuclear positioning and coregulator expression. Nucl. Recept Signal 2009, 7:e009.
42. Shatnawi A., Tran T., Ratnam M. R5020 and RU486 act as progesterone receptor agonists to enhance Sp1/Sp4-dependent gene transcription by an indirect mechanism. Mol. Endocrinol. 2007, 21:635-650.
43. Skildum A., Faivre E., Lange C.A. Progesterone receptors induce cell cycle progression via activation of mitogen-activated protein kinases. Mol. Endocrinol. 2005, 19:327-339.
44. Sorlie T., Perou C.M., Tibshirani R., Aas T., Geisler S., Johnsen H., Hastie T., Eisen M.B., van de Rijn M., Jeffrey S.S., et al. Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc. Natl. Acad. Sci. U.S.A. 2001, 98:10869-10874.
45. Spitz I.M. Progesterone receptor antagonists. Curr. Opin. Invest. Drugs 2006, 7:882-890.
46. Takahashi A., Kato K., Kuboyama A., Inoue T., Tanaka Y., Kuhara A., Kinoshita K., Takeda S., Wake N. Induction of senescence by progesterone receptor-B activation in response to cAMP in ovarian cancer cells. Gynecol. Oncol. 2009, 113:270-276.
47. Wiechert R., Neef G. Synthesis of antiprogestational steroids. J. Steroid Biochem. 1987, 27:851-858.