Role of progesterone in endometrial cancer

Seminars in Reproductive Medicine

Volumn 28, Issue 1, 2010, Pages 81-90

  Kim, J Julie ^a   Chapman Davis, Eloise ^a,b  

^a NORTHWESTERN UNIVERSITY   (United States)

^b NORTHWESTERN UNIVERSITY   (United States)

Author keywords

Endometrial cancer; Progesterone; Progesterone receptor; Uterus

Indexed keywords

ALPHA3 INTEGRIN; BETA1 INTEGRIN; BETA3 INTEGRIN; CATECHOL METHYLTRANSFERASE; CYCLIN D1; ESTROGEN; ESTROGEN RECEPTOR; FIBRONECTIN; GELATINASE A; GELATINASE B; GESTAGEN; HYDROXYPROGESTERONE CAPROATE; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERSTITIAL COLLAGENASE; LEVONORGESTREL; MATRILYSIN; MEDROXYPROGESTERONE ACETATE; MEGESTROL ACETATE; PROGESTERONE; PROGESTERONE RECEPTOR; PROGESTERONE RECEPTOR A; PROGESTERONE RECEPTOR B; PROTEIN BAX; PROTEIN BCL 2; PROTEIN P21; PROTEIN P27; TRANSCRIPTION FACTOR AP 1; TRANSCRIPTION FACTOR FKHR;

CANCER CELL; CELL FUNCTION; DRUG EFFICACY; DRUG MEGADOSE; ENDOMETRIUM CANCER; ENDOMETRIUM CARCINOMA; ENDOMETRIUM HYPERPLASIA; ESTROGEN ACTIVITY; GENE CONTROL; HORMONAL THERAPY; HUMAN; LOW DRUG DOSE; REVIEW; TREATMENT INDICATION;

ANIMALS; ENDOMETRIAL NEOPLASMS; ENDOMETRIUM; FEMALE; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MICE; PROGESTERONE; PROGESTINS; RECEPTORS, PROGESTERONE;

EID: 76249116000     PISSN: 15268004     EISSN: 15264564     Source Type: Journal    
DOI: 10.1055/s-0029-1242998     Document Type: Review

References (85)

1. Kurita T, Nakamura H. Embryology and Anatomy of the Uterus. 2nd ed. Newark, NJ Harwood Academic 2007
2. Clarke C L., Sutherland R L. Progestin regulation of cellular proliferation. Endocr Rev 1990 11 (2) 266-301
3. Dockery P, Li T C., Rogers A W., Cooke I D., Lenton E A. The ultrastructure of the glandular epithelium in the timed endometrial biopsy. Hum Reprod 1988 3 (7) 826-834
4. Wynn R M. Ultrastructural development of the human decidua. Am J Obstet Gynecol 1974 118 (5) 652-670
5. Gellersen B, Brosens J. Cyclic AMP and progesterone receptor cross-talk in human endometrium: a decidualizing affair. J Endocrinol 2003 178 (3) 357-372
6. Mulac-Jericevic B, Mullinax R A., DeMayo F J., Lydon J P., Conneely O M. Subgroup of reproductive functions of progesterone mediated by progesterone receptor-B isoform. Science 2000 289 (5485) 1751-1754
7. Gronemeyer H, Meyer M E., Bocquel M T., Kastner P, Turcotte B, Chambon P. Progestin receptors: isoforms and antihormone action. J Steroid Biochem Mol Biol 1991 40 (1-3) 271-278
8. 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 (5) 1603-1614
9. Lessey B A., Alexander P S., Horwitz K B. The subunit structure of human breast cancer progesterone receptors: characterization by chromatography and photoaffinity labeling. Endocrinology 1983 112 (4) 1267-1274
10. Chi T, Lieberman P, Ellwood K, Carey M. A general mechanism for transcriptional synergy by eukaryotic activators. Nature 1995 377 (6546) 254-257
11. Giangrande P H., Kimbrel E A., Edwards D P., McDonnell D P. The opposing transcriptional activities of the two isoforms of the human progesterone receptor are due to differential cofactor binding. Mol Cell Biol 2000 20 (9) 3102-3115
12. McDonnell D P., Shahbaz M M., Vegeto E, Goldman M E. The human progesterone receptor A-form functions as a transcriptional modulator of mineralocorticoid receptor transcriptional activity. J Steroid Biochem Mol Biol 1994 48 (5-6) 425-432
13. Tetel M J., Giangrande P H., Leonhardt S A., McDonnell D P., Edwards D P. Hormone-dependent interaction between the amino-and carboxyl-terminal domains of progesterone receptor in vitro and in vivo. Mol Endocrinol 1999 13 (6) 910-924
14. Tung L, Abdel-Hafiz H, Shen T et al. Progesterone receptors (PR)-B and-A regulate transcription by different mechanisms: AF-3 exerts regulatory control over coactivator binding to PR-B. Mol Endocrinol 2006 20 (11) 2656-2670
15. Tung L, Mohamed M K., Hoeffler J P., Takimoto G S., Horwitz K B. Antagonist-occupied human progesterone B-receptors activate transcription without binding to progesterone response elements and are dominantly inhibited by A-receptors. Mol Endocrinol 1993 7 (10) 1256-1265
16. Vegeto E, Shahbaz M M., Wen D X., Goldman M E., O'Malley B W., McDonnell D P. Human progesterone receptor A form is a cell-and promoter-specific repressor of human progesterone receptor B function. Mol Endocrinol 1993 7 (10) 1244-1255
17. Wagner B L., Norris J D., Knotts T A., Weigel N L., McDonnell D P. The nuclear corepressors NCoR and SMRT are key regulators of both ligand-and 8-bromo-cyclic AMP-dependent transcriptional activity of the human progesterone receptor. Mol Cell Biol 1998 18 (3) 1369-1378
18. Mangal R K., Wiehle R D., Poindexter A N. III, Weigel N L. Differential expression of uterine progesterone receptor forms A and B during the menstrual cycle. J Steroid Biochem Mol Biol 1997 63 (4-6) 195-202
19. Garcia E, Bouchard P, De Brux J et al. Use of immunocytochemistry of progesterone and estrogen receptors for endometrial dating. J Clin Endocrinol Metab 1988 67 (1) 80-87
20. Mylonas I, Jeschke U, Shabani N et al. Steroid receptors ERalpha, ERbeta, PR-A and PR-B are differentially expressed in normal and atrophic human endometrium. Histol Histopathol 2007 22 (2) 169-176
21. Snijders M P., de Goeij A F., Debets-Te Baerts M J., Rousch M J., Koudstaal J, Bosman F T. Immunocytochemical analysis of oestrogen receptors and progesterone receptors in the human uterus throughout the menstrual cycle and after the menopause. J Reprod Fertil 1992 94 (2) 363-371
22. American Cancer Society. Cancer facts and figures. Atlanta, GA American Cancer Society 2008
23. Creasman W T. Endometrial cancer: incidence, prognostic factors, diagnosis, and treatment. Semin Oncol 1997 24 (1, Suppl 1) 140-150
24. Münstedt K, Grant P, Woenckhaus J, Roth G, Tinneberg H R. Cancer of the endometrium: current aspects of diagnostics and treatment. World J Surg Oncol 2004 2 24
25. Sherman M E. Theories of endometrial carcinogenesis: a multidisciplinary approach. Mod Pathol 2000 13 (3) 295-308
26. Gallup D G., Stock R J. Adenocarcinoma of the endometrium in women 40 years of age or younger. Obstet Gynecol 1984 64 (3) 417-420
27. Trimble C L., Kauderer J, Zaino R et al. Concurrent endometrial carcinoma in women with a biopsy diagnosis of atypical endometrial hyperplasia: a Gynecologic Oncology Group study. Cancer 2006 106 (4) 812-819 (Pubitemid 43238448)
28. Reifenstein E C. Jr. The treatment of advanced endometrial cancer with hydroxyprogesterone caproate. Gynecol Oncol 1974 2 (2-3) 377-414
29. Saegusa M, Okayasu I. Progesterone therapy for endometrial carcinoma reduces cell proliferation but does not alter apoptosis. Cancer 1998 83 (1) 111-121
30. Affinito P, Di Carlo C, Di Mauro P, Napolitano V, Nappi C. Endometrial hyperplasia: efficacy of a new treatment with a vaginal cream containing natural micronized progesterone. Maturitas 1994 20 (2-3) 191-198
31. Clark T J., Neelakantan D, Gupta J K. The management of endometrial hyperplasia: an evaluation of current practice. Eur J Obstet Gynecol Reprod Biol 2006 125 (2) 259-264
32. Ferenczy A, Gelfand M. The biologic significance of cytologic atypia in progestogen-treated endometrial hyperplasia. Am J Obstet Gynecol 1989 160 (1) 126-131
33. Gal D, Edman C D., Vellios F, Forney J P. Long-term effect of megestrol acetate in the treatment of endometrial hyperplasia. Am J Obstet Gynecol 1983 146 (3) 316-322
34. Varma R, Soneja H, Bhatia K et al. The effectiveness of a levonorgestrel-releasing intrauterine system (LNG-IUS) in the treatment of endometrial hyperplasiaa long-term follow-up study. Eur J Obstet Gynecol Reprod Biol 2008 139 (2) 169-175
35. Randall T C., Kurman R J. Progestin treatment of atypical hyperplasia and well-differentiated carcinoma of the endometrium in women under age 40. Obstet Gynecol 1997 90 (3) 434-440
36. Wheeler D T., Bristow R E., Kurman R J. Histologic alterations in endometrial hyperplasia and well-differentiated carcinoma treated with progestins. Am J Surg Pathol 2007 31 (7) 988-998
37. Ushijima K, Yahata H, Yoshikawa H et al. Multicenter phase II study of fertility-sparing treatment with medroxyprogesterone acetate for endometrial carcinoma and atypical hyperplasia in young women. J Clin Oncol 2007 25 (19) 2798-2803
38. Ramirez P T., Frumovitz M, Bodurka D C., Sun C C., Levenback C. Hormonal therapy for the management of grade 1 endometrial adenocarcinoma: a literature review. Gynecol Oncol 2004 95 (1) 133-138
39. Chiva L, Lapuente F, González-Cortijo L et al. Sparing fertility in young patients with endometrial cancer. Gynecol Oncol 2008 111 (2, Suppl) S101-S104
40. Kim Y B., Holschneider C H., Ghosh K, Nieberg R K., Montz F J. Progestin alone as primary treatment of endometrial carcinoma in premenopausal women. Report of seven cases and review of the literature. Cancer 1997 79 (2) 320-327
41. Montz F J., Bristow R E., Bovicelli A, Tomacruz R, Kurman R J. Intrauterine progesterone treatment of early endometrial cancer. Am J Obstet Gynecol 2002 186 (4) 651-657
42. Dhar K K., NeedhiRajan T, Koslowski M, Woolas R P. Is levonorgestrel intrauterine system effective for treatment of early endometrial cancer? Report of four cases and review of the literature. Gynecol Oncol 2005 97 (3) 924-927
43. Jones K, Georgiou M, Hyatt D, Spencer T, Thomas H. Endometrial adenocarcinoma following the insertion of a Mirena IUCD. Gynecol Oncol 2002 87 (2) 216-218
44. Kresowik J, Ryan G L., Van Voorhis B J. Progression of atypical endometrial hyperplasia to adenocarcinoma despite intrauterine progesterone treatment with the levonorgestrel-releasing intrauterine system. Obstet Gynecol 2008 111 (2 Pt 2) 547-549
45. Kelley R M., Baker W H. Progestational agents in the treatment of carcinoma of the endometrium. N Engl J Med 1961 264 216-222
46. Piver M S., Barlow J J., Lurain J R., Blumenson L E. Medroxyprogesterone acetate (Depo-Provera) vs. hydroxyprogesterone caproate (Delalutin) in women with metastatic endometrial adenocarcinoma. Cancer 1980 45 (2) 268-272
47. Decruze S B., Green J A. Hormone therapy in advanced and recurrent endometrial cancer: a systematic review. Int J Gynecol Cancer 2007 17 (5) 964-978
48. Thigpen J T., Brady M F., Alvarez R D. et al. Oral medroxyprogesterone acetate in the treatment of advanced or recurrent endometrial carcinoma: a dose-response study by the Gynecologic Oncology Group. J Clin Oncol 1999 17 (6) 1736-1744
49. Markman M. Hormonal therapy of endometrial cancer. Eur J Cancer 2005 41 (5) 673-675
50. Quinn M A., Cauchi M, Fortune D. Endometrial carcinoma: steroid receptors and response to medroxyprogesterone acetate. Gynecol Oncol 1985 21 (3) 314-319
51. Ehrlich C E., Young P C., Stehman F B., Sutton G P., Alford W M. Steroid receptors and clinical outcome in patients with adenocarcinoma of the endometrium. Am J Obstet Gynecol 1988 158 (4) 796-807
52. Leslie K K., Stein M P., Kumar N S. et al. Progesterone receptor isoform identification and subcellular localization in endometrial cancer. Gynecol Oncol 2005 96 (1) 32-41
53. Fujimoto J, Ichigo S, Hori M, Nishigaki M, Tamaya T. Expression of progesterone receptor form A and B mRNAs in gynecologic malignant tumors. Tumour Biol 1995 16 (4) 254-260
54. Arnett-Mansfield R L., deFazio A, Wain G V. et al. Relative expression of progesterone receptors A and B in endometrioid cancers of the endometrium. Cancer Res 2001 61 (11) 4576-4582
55. Kumar N S., Richer J, Owen G, Litman E, Horwitz K B., Leslie K K. Selective down-regulation of progesterone re+Although+ceptor isoform B in poorly differentiated human endometrial cancer cells: implications for unopposed estrogen action. Cancer Res 1998 58 (9) 1860-1865
56. Jongen V, Briët J, de Jong R et al. Expression of estrogen receptor-alpha and-beta and progesterone receptor-A and-B in a large cohort of patients with endometrioid endometrial cancer. Gynecol Oncol 2009 112 (3) 537-542
57. Zheng W, Baker H E., Mutter G L. Involution of PTEN-null endometrial glands with progestin therapy. Gynecol Oncol 2004 92 (3) 1008-1013
58. Mutter G L., Lin M C., Fitzgerald J T. et al. Altered PTEN expression as a diagnostic marker for the earliest endometrial precancers. J Natl Cancer Inst 2000 92 (11) 924-930
59. Francis L W., Lewis P D., Gonzalez D et al. Progesterone induces nano-scale molecular modifications on endometrial epithelial cell surfaces. Biol Cell 2009 101 (8) 481-491
60. Dai D, Wolf D M., Litman E S., White M J., Leslie K K. Progesterone inhibits human endometrial cancer cell growth and invasiveness: down-regulation of cellular adhesion molecules through progesterone B receptors. Cancer Res 2002 62 (3) 881-886
61. Ueda M, Fujii H, Yoshizawa K, Abe F, Ueki M. Effects of sex steroids and growth factors on migration and invasion of endometrial adenocarcinoma SNG-M cells in vitro. Jpn J Cancer Res 1996 87 (5) 524-533
62. Smid-Koopman E, Blok L J., Kühne L C. et al. Distinct functional differences of human progesterone receptors A and B on gene expression and growth regulation in two endometrial carcinoma cell lines. J Soc Gynecol Investig 2003 10 (1) 49-57
63. Hanekamp E E., Kühne L M., Grootegoed J A., Burger C W., Blok L J. Progesterone receptor A and B expression and progestagen treatment in growth and spread of endometrial cancer cells in nude mice. Endocr Relat Cancer 2004 11 (4) 831-841
64. Saito T, Mizumoto H, Tanaka R et al. Overexpressed progesterone receptor form B inhibit invasive activity suppressing matrix metalloproteinases in endometrial carcinoma cells. Cancer Lett 2004 209 (2) 237-243
65. Di Nezza L A., Jobling T, Salamonsen L A. Progestin suppresses matrix metalloproteinase production in endometrial cancer. Gynecol Oncol 2003 89 (2) 325-333
66. Jaffe R C., Ferguson-Gottschall S D., Gao W, Beam C, Fazleabas A T. Histone deacetylase inhibition and progesterone act synergistically to stimulate baboon glycodelin gene expression. J Mol Endocrinol 2007 38 (3) 401-407
67. Uchida H, Maruyama T, Nagashima T, Asada H, Yoshimura Y. Histone deacetylase inhibitors induce differentiation of human endometrial adenocarcinoma cells through up-regulation of glycodelin. Endocrinology 2005 146 (12) 5365-5373
68. Uchida H, Maruyama T, Ono M et al. Histone deacetylase inhibitors stimulate cell migration in human endometrial adenocarcinoma cells through up-regulation of glycodelin. Endocrinology 2007 148 (2) 896-902
69. Ohta K, Maruyama T, Uchida H et al. Glycodelin blocks progression to S phase and inhibits cell growth: a possible progesterone-induced regulator for endometrial epithelial cell growth. Mol Hum Reprod 2008 14 (1) 17-22
70. Dai D, Kumar N S., Wolf D M., Leslie K K. Molecular tools to reestablish progestin control of endometrial cancer cell proliferation. Am J Obstet Gynecol 2001 184 (5) 790-797
71. Ward E C., Hoekstra A V., Blok L J. et al. The regulation and function of the forkhead transcription factor, Forkhead box O1, is dependent on the progesterone receptor in endometrial carcinoma. Endocrinology 2008 149 (4) 1942-1950
72. Goto T, Takano M, Albergaria A et al. Mechanism and functional consequences of loss of FOXO1 expression in endometrioid endometrial cancer cells. Oncogene 2008 27 (1) 9-19
73. Shiozawa T, Nikaido T, Nakayama K, Lu X, Fujii S. Involvement of cyclin-dependent kinase inhibitor p27Kip1 in growth inhibition of endometrium in the secretory phase and of hyperplastic endometrium treated with progesterone. Mol Hum Reprod 1998 4 (9) 899-905
74. Watanabe J, Watanabe K, Jobo T et al. Significance of p27 as a predicting marker for medroxyprogesterone acetate therapy against endometrial endometrioid adenocarcinoma. Int J Gynecol Cancer 2006 16 (Suppl 1) 452-457
75. Vereide A B., Kaino T, Sager G, ∅rbo A, Scottish Gynaecological Clinical Trials Group. Bcl-2, BAX, and apoptosis in endometrial hyperplasia after high dose gestagen therapy: a comparison of responses in patients treated with intrauterine levonorgestrel and systemic medroxyprogesterone. Gynecol Oncol 2005 97 (3) 740-750
76. Paulssen R H., Moe B, Grønaas H, Orbo A. Gene expression in endometrial cancer cells (Ishikawa) after short time high dose exposure to progesterone. Steroids 2008 73 (1) 116-128
77. Hanekamp E E., Kühne E C., Smid-Koopman E et al. Loss of progesterone receptor may lead to an invasive phenotype in human endometrial cancer. Eur J Cancer 2002 38 (Suppl 6) S71-S72
78. Davies S, Dai D, Wolf D M., Leslie K K. Immunomodulatory and transcriptional effects of progesterone through progesterone A and B receptors in Hec50co poorly differentiated endometrial cancer cells. J Soc Gynecol Investig 2004 11 (7) 494-499
79. Dai D, Litman E S., Schonteich E, Leslie K K. Progesterone regulation of activating protein-1 transcriptional activity: a possible mechanism of progesterone inhibition of endometrial cancer cell growth. J Steroid Biochem Mol Biol 2003 87 (2-3) 123-131
80. Davies S, Dai D, Feldman I, Pickett G, Leslie K K. Identification of a novel mechanism of NF-kappaB inactivation by progesterone through progesterone receptors in Hec50co poorly differentiated endometrial cancer cells: induction of A20 and ABIN-2. Gynecol Oncol 2004 94 (2) 463-470
81. Salih S M., Salama S A., Jamaluddin M et al. Progesterone-mediated regulation of catechol-O-methyl transferase expression in endometrial cancer cells. Reprod Sci 2008 15 (2) 210-220
82. Tamura M, Sebastian S, Yang S et al. Up-regulation of cyclooxygenase-2 expression and prostaglandin synthesis in endometrial stromal cells by malignant endometrial epithelial cells. A paracrine effect mediated by prostaglandin E2 and nuclear factor-kappa B. J Biol Chem 2002 277 (29) 26208-26216
83. Yang S, Fang Z, Gurates B et al. Stromal PRs mediate induction of 17beta-hydroxysteroid dehydrogenase type 2 expression in human endometrial epithelium: a paracrine mechanism for inactivation of E2. Mol Endocrinol 2001 15 (12) 2093-2105
84. Lee K, Jeong J, Tsai M J. et al. Molecular mechanisms involved in progesterone receptor regulation of uterine function. J Steroid Biochem Mol Biol 2006 102 (1) 41-50
85. 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 (11) 5872-5887