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BMC Cancer
Published in: BMC Cancer 1/2009

Open Access 01-12-2009 | Research article

Expression of oestrogen receptors, ERα, ERβ, and ERβ variants, in endometrial cancers and evidence that prostaglandin F may play a role in regulating expression of ERα

Authors: Frances Collins, Sheila MacPherson, Pamela Brown, Vincent Bombail, Alistair RW Williams, Richard A Anderson, Henry N Jabbour, Philippa TK Saunders

Published in: BMC Cancer | Issue 1/2009

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Abstract

Background

Endometrial cancer is the most common gynaecological malignancy; risk factors include exposure to oestrogens and high body mass index. Expression of enzymes involved in biosynthesis of oestrogens and prostaglandins (PG) is often higher in endometrial cancers when compared with levels detected in normal endometrium. Oestrogens bind one of two receptors (ERα and ERβ) encoded by separate genes. The full-length receptors function as ligand-activated transcription factors; splice variant isoforms of ERβ lacking a ligand-binding domain have also been described. PGs act in an autocrine or paracrine manner by binding to specific G-protein coupled receptors.

Methods

We compared expression of ERs, progesterone receptor (PR) and cyclooxygenase-2 (COX-2) in stage 1 endometrial adenocarcinomas graded as well (G1), moderately (G2) or poorly (G3) differentiated (n ≥ 10 each group) using qRTPCR, single and double immunohistochemistry. We used endometrial adenocarcinoma cell lines to investigate the impact of PGF2α on expression of ERs and PR.

Results

Full length ERβ (ERβ1) and two ERβ variants (ERβ2, ERβ5) were expressed in endometrial cancers regardless of grade and the proteins were immunolocalised to the nuclei of cells in both epithelial and stromal compartments. Immunoexpression of COX-2 was most intense in cells that were ERαneg/low. Expression of PR in endometrial adenocarcinoma (Ishikawa) cell lines and tissues broadly paralleled that of ERα. Treatment of adenocarcinoma cells with PGF2α reduced expression of ERα but had no impact on ERβ1. Cells incubated with PGF2α were unable to increase expression of PR mRNA when they were incubated with E2.

Conclusion

We have demonstrated that ERβ5 protein is expressed in stage 1 endometrial adenocarcinomas. Expression of three ERβ variants, including the full-length protein is not grade-dependent and most cells in poorly differentiated cancers are ERβpos/ERαneg. We found evidence of a link between COX-2, its product PGF2α, and expression of ERα and PR that sheds new light on the cross talk between steroid and PG signalling pathways in this disease.
Appendix
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Literature
1.
Shapiro S, Kelly JP, Rosenberg L, Kaufman DW, Helmrich SP, Rosenshein NB, Lewis JL, Knapp RC, Stolley PD, Schottenfeld D: Risk of localized and widespread endometrial cancer in relation to recent and discontinued use of conjugated estrogens. N Engl J Med. 1985, 313 (16): 969-972.CrossRefPubMed
2.
Beral V, Bull D, Reeves G: Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005, 365 (9470): 1543-1551. 10.1016/S0140-6736(05)66455-0.CrossRefPubMed
3.
Hale GE, Hughes CL, Cline JM: Endometrial cancer: hormonal factors, the perimenopausal "window of risk," and isoflavones. J Clin Endocrinol Metab. 2002, 87 (1): 3-15. 10.1210/jc.87.1.3.PubMed
4.
Rieck G, Fiander A: The effect of lifestyle factors on gynaecological cancer. Best Pract Res Clin Obstet Gynaecol. 2006, 20 (2): 227-251. 10.1016/j.bpobgyn.2005.10.010.CrossRefPubMed
5.
Bergstrom A, Pisani P, Tenet V, Wolk A, Adami HO: Overweight as an avoidable cause of cancer in Europe. Int J Cancer. 2001, 91 (3): 421-430. 10.1002/1097-0215(200002)9999:9999<::AID-IJC1053>3.0.CO;2-T.CrossRefPubMed
6.
Gates EJ, Hirschfield L, Matthews RP, Yap OW: Body mass index as a prognostic factor in endometrioid adenocarcinoma of the endometrium. J Natl Med Assoc. 2006, 98 (11): 1814-1822.PubMedPubMedCentral
7.
Bulun SE, Economos K, Miller D, Simpson ER: CYP19 (aromatase cytochrome P450) gene expression in human malignant endometrial tumors. J Clin Endocrinol Metab. 1994, 79 (6): 1831-1834. 10.1210/jc.79.6.1831.PubMed
8.
Utsunomiya H, Suzuki T, Kaneko C, Takeyama J, Nakamura J, Kimura K, Yoshihama M, Harada N, Ito K, Konno R, et al: The analyses of 17beta-hydroxysteroid dehydrogenase isozymes in human endometrial hyperplasia and carcinoma. J Clin Endocrinol Metab. 2001, 86 (7): 3436-3443. 10.1210/jc.86.7.3436.PubMed
9.
Berstein LM, Tchernobrovkina AE, Gamajunova VB, Kovalevskij AJ, Vasilyev DA, Chepik OF, Turkevitch EA, Tsyrlina EV, Maximov SJ, Ashrafian LA, et al: Tumor estrogen content and clinico-morphological and endocrine features of endometrial cancer. J Cancer Res Clin Oncol. 2003, 129 (4): 245-249.PubMed
10.
Leung YK, Mak P, Hassan S, Ho SM: Estrogen receptor (ER)-beta isoforms: a key to understanding ER-beta signaling. Proc Natl Acad Sci USA. 2006, 103 (35): 13162-13167. 10.1073/pnas.0605676103.CrossRefPubMedPubMedCentral
11.
Critchley HO, Brenner RM, Henderson TA, Williams K, Nayak NR, Slayden OD, Millar MR, Saunders PT: Estrogen receptor beta, but not estrogen receptor alpha, is present in the vascular endothelium of the human and nonhuman primate endometrium. J Clin Endocrinol Metab. 2001, 86 (3): 1370-1378. 10.1210/jc.86.3.1370.PubMed
12.
Critchley HO, Henderson TA, Kelly RW, Scobie GS, Evans LR, Groome NP, Saunders PT: Wild-type estrogen receptor (ERbeta1) and the splice variant (ERbetacx/beta2) are both expressed within the human endometrium throughout the normal menstrual cycle. J Clin Endocrinol Metab. 2002, 87 (11): 5265-5273. 10.1210/jc.2002-020502.CrossRefPubMed
13.
Savouret JF, Bailly A, Misrahi M, Rauch C, Redeuilh G, Chauchereau A, Milgrom E: Characterization of the hormone responsive element involved in the regulation of the progesterone receptor gene. Embo J. 1991, 10 (7): 1875-1883.PubMedPubMedCentral
14.
Kauppila AJ, Isotalo HE, Kivinen ST, Vihko RK: Prediction of clinical outcome with estrogen and progestin receptor concentrations and their relationships to clinical and histopathological variables in endometrial cancer. Cancer Res. 1986, 46 (10): 5380-5384.PubMed
15.
Utsunomiya H, Suzuki T, Harada N, Ito K, Matsuzaki S, Konno R, Sato S, Yajima A, Sasano H: Analysis of estrogen receptor alpha and beta in endometrial carcinomas: correlation with ER beta and clinicopathologic findings in 45 cases. Int J Gynecol Pathol. 2000, 19 (4): 335-341. 10.1097/00004347-200010000-00007.CrossRefPubMed
16.
Skrzypczak M, Bieche I, Szymczak S, Tozlu S, Lewandowski S, Girault I, Radwanska K, Szczylik C, Jakowicki JA, Lidereau R, et al: Evaluation of mRNA expression of estrogen receptor beta and its isoforms in human normal and neoplastic endometrium. Int J Cancer. 2004, 110 (6): 783-787. 10.1002/ijc.20224.CrossRefPubMed
17.
Chakravarty D, Srinivasan R, Ghosh S, Gopalan S, Rajwanshi A, Majumdar S: Estrogen receptor beta1 and the beta2/betacx isoforms in nonneoplastic endometrium and in endometrioid carcinoma. Int J Gynecol Cancer. 2007, 17 (4): 905-913. 10.1111/j.1525-1438.2006.00851.x.CrossRefPubMed
18.
Fukuda K, Mori M, Uchiyama M, Iwai K, Iwasaka T, Sugimori H: Prognostic significance of progesterone receptor immunohistochemistry in endometrial carcinoma. Gynecol Oncol. 1998, 69 (3): 220-225. 10.1006/gyno.1998.5023.CrossRefPubMed
19.
Ito K, Utsunomiya H, Yaegashi N, Sasano H: Biological Roles of Estrogen and Progesterone in Human Endometrial Carcinoma - New developments in potential endocrine therapy for endometrial cancer. Endocr J. 2007, 54 (5): 667-679. 10.1507/endocrj.KR-114.CrossRefPubMed
20.
Hofer G, Bieglmayer C, Kopp B, Janisch H: Measurement of eicosanoids in menstrual fluid by the combined use of high pressure chromatography and radioimmunoassay. Prostaglandins. 1993, 45 (5): 413-426. 10.1016/0090-6980(93)90118-Q.CrossRefPubMed
21.
Jabbour HN, Sales KJ: Prostaglandin receptor signalling and function in human endometrial pathology. Trends Endocrinol Metab. 2004, 15 (8): 398-404.CrossRefPubMed
22.
Tamura M, Deb S, Sebastian S, Okamura K, Bulun SE: Estrogen up-regulates cyclooxygenase-2 via estrogen receptor in human uterine microvascular endothelial cells. Fertil Steril. 2004, 81 (5): 1351-1356. 10.1016/j.fertnstert.2003.09.076.CrossRefPubMed
23.
Punyadeera C, Dunselman G, Marbaix E, Kamps R, Galant C, Nap A, Goeij A, Ederveen A, Groothuis P: Triphasic pattern in the ex vivo response of human proliferative phase endometrium to oestrogens. J Steroid Biochem Mol Biol. 2004, 92 (3): 175-185. 10.1016/j.jsbmb.2004.06.005.CrossRefPubMed
24.
Frasor J, Weaver AE, Pradhan M, Mehta K: Synergistic up-regulation of prostaglandin E synthase expression in breast cancer cells by 17beta-estradiol and proinflammatory cytokines. Endocrinology. 2008, 149 (12): 6272-6279. 10.1210/en.2008-0352.CrossRefPubMed
25.
Bulun SE, Fang Z, Imir G, Gurates B, Tamura M, Yilmaz B, Langoi D, Amin S, Yang S, Deb S: Aromatase and endometriosis. Semin Reprod Med. 2004, 22 (1): 45-50. 10.1055/s-2004-823026.CrossRefPubMed
26.
Brueggemeier RW, Su B, Sugimoto Y, Diaz-Cruz ES, Davis DD: Aromatase and COX in breast cancer: enzyme inhibitors and beyond. J Steroid Biochem Mol Biol. 2007, 106 (1-5): 16-23. 10.1016/j.jsbmb.2007.05.021.CrossRefPubMedPubMedCentral
27.
Jabbour HN, Milne SA, Williams AR, Anderson RA, Boddy SC: Expression of COX-2 and PGE synthase and synthesis of PGE(2)in endometrial adenocarcinoma: a possible autocrine/paracrine regulation of neoplastic cell function via EP2/EP4 receptors. Br J Cancer. 2001, 85 (7): 1023-1031.CrossRefPubMed
28.
Uotila PJ, Erkkola RU, Klemi PJ: The expression of cyclooxygenase-1 and -2 in proliferative endometrium and endometrial adenocarcinoma. Ann Med. 2002, 34 (6): 428-433. 10.1080/078538902321012379.CrossRefPubMed
29.
Jabbour HN, Sales KJ, Boddy SC, Anderson RA, Williams AR: A positive feedback loop that regulates cyclooxygenase-2 expression and prostaglandin F2alpha synthesis via the F-series-prostanoid receptor and extracellular signal-regulated kinase 1/2 signaling pathway. Endocrinology. 2005, 146 (11): 4657-4664. 10.1210/en.2005-0804.CrossRefPubMed
30.
Sales KJ, Boddy SC, Williams AR, Anderson RA, Jabbour HN: F-prostanoid receptor regulation of fibroblast growth factor 2 signaling in endometrial adenocarcinoma cells. Endocrinology. 2007, 148 (8): 3635-3644. 10.1210/en.2006-1517.CrossRefPubMed
31.
Sales KJ, List T, Boddy SC, Williams AR, Anderson RA, Naor Z, Jabbour HN: A novel angiogenic role for prostaglandin F2alpha-FP receptor interaction in human endometrial adenocarcinomas. Cancer Res. 2005, 65 (17): 7707-7716.PubMedPubMedCentral
32.
Milne SA, Jabbour HN: Prostaglandin (PG) F(2alpha) receptor expression and signaling in human endometrium: role of PGF(2alpha) in epithelial cell proliferation. J Clin Endocrinol Metab. 2003, 88 (4): 1825-1832. 10.1210/jc.2002-021368.CrossRefPubMed
33.
Scully R, Bonfiglio T, Kurman R, Silverberg S, Wilkinson E: Histological Typing of Female Genital Tract Tumours. 1994, Berlin: Springer Verlag, 2CrossRef
34.
Nishida M, Kasahara K, Kaneko M, Iwasaki H, Hayashi K: [Establishment of a new human endometrial adenocarcinoma cell line, Ishikawa cells, containing estrogen and progesterone receptors]. Nippon Sanka Fujinka Gakkai Zasshi. 1985, 37 (7): 1103-1111.PubMed
35.
Ignar-Trowbridge DM, Teng CT, Ross KA, Parker MG, Korach KS, McLachlan JA: Peptide growth factors elicit estrogen receptor-dependent transcriptional activation of an estrogen-responsive element. Mol Endocrinol. 1993, 7 (8): 992-998. 10.1210/me.7.8.992.PubMed
36.
Hall JM, McDonnell DP: The estrogen receptor beta-isoform (ERbeta) of the human estrogen receptor modulates ERalpha transcriptional activity and is a key regulator of the cellular response to estrogens and antiestrogens. Endocrinology. 1999, 140 (12): 5566-5578. 10.1210/en.140.12.5566.PubMed
37.
Sierens JE, Scobie GA, Wilson J, Saunders PT: Cloning of oestrogen receptor beta from Old and New World primates: identification of splice variants and functional analysis. J Mol Endocrinol. 2004, 32 (3): 703-718. 10.1677/jme.0.0320703.CrossRefPubMed
38.
Saunders PT, Millar MR, Macpherson S, Irvine DS, Groome NP, Evans LR, Sharpe RM, Scobie GA: ERbeta1 and the ERbeta2 splice variant (ERbetacx/beta2) are expressed in distinct cell populations in the adult human testis. J Clin Endocrinol Metab. 2002, 87 (6): 2706-2715. 10.1210/jc.87.6.2706.PubMed
39.
Shaaban AM, Green AR, Karthik S, Alizadeh Y, Hughes TA, Harkins L, Ellis IO, Robertson JF, Paish EC, Saunders PT, et al: Nuclear and cytoplasmic expression of ERbeta1, ERbeta2, and ERbeta5 identifies distinct prognostic outcome for breast cancer patients. Clin Cancer Res. 2008, 14 (16): 5228-5235. 10.1158/1078-0432.CCR-07-4528.CrossRefPubMed
40.
Anderson RA, Fulton N, Cowan G, Coutts S, Saunders PT: Conserved and divergent patterns of expression of DAZL, VASA and OCT4 in the germ cells of the human fetal ovary and testis. BMC Dev Biol. 2007, 7 (1): 136-10.1186/1471-213X-7-136.CrossRefPubMedPubMedCentral
41.
Sales KJ, Milne SA, Williams AR, Anderson RA, Jabbour HN: Expression, localization, and signaling of prostaglandin F2 alpha receptor in human endometrial adenocarcinoma: regulation of proliferation by activation of the epidermal growth factor receptor and mitogen-activated protein kinase signaling pathways. J Clin Endocrinol Metab. 2004, 89 (2): 986-993. 10.1210/jc.2003-031434.CrossRefPubMed
42.
Setiawan VW, Doherty JA, Shu XO, Akbari MR, Chen C, De Vivo I, Demichele A, Garcia-Closas M, Goodman MT, Haiman CA, et al: Two estrogen-related variants in CYP19A1 and endometrial cancer risk: a pooled analysis in the Epidemiology of Endometrial Cancer Consortium. Cancer Epidemiol Biomarkers Prev. 2009, 18 (1): 242-247. 10.1158/1055-9965.EPI-08-0689.CrossRefPubMedPubMedCentral
43.
Scobie GA, Macpherson S, Millar MR, Groome NP, Romana PG, Saunders PT: Human oestrogen receptors: differential expression of ER alpha and beta and the identification of ER beta variants. Steroids. 2002, 67 (12): 985-992. 10.1016/S0039-128X(02)00047-8.CrossRefPubMed
44.
Kleine W, Maier T, Geyer H, Pfleiderer A: Estrogen and progesterone receptors in endometrial cancer and their prognostic relevance. Gynecol Oncol. 1990, 38 (1): 59-65. 10.1016/0090-8258(90)90012-A.CrossRefPubMed
45.
Frasor J, Barnett DH, Danes JM, Hess R, Parlow AF, Katzenellenbogen BS: Response-specific and ligand dose-dependent modulation of estrogen receptor (ER) alpha activity by ERbeta in the uterus. Endocrinology. 2003, 144 (7): 3159-3166. 10.1210/en.2002-0143.CrossRefPubMed
46.
Horree N, van Diest PJ, Groep van der P, Sie-Go DM, Heintz AP: Progressive derailment of cell cycle regulators in endometrial carcinogenesis. J Clin Pathol. 2008, 61 (1): 36-42. 10.1136/jcp.2006.043794.CrossRefPubMed
47.
Ferrandina G, Ranelletti FO, Gallotta V, Martinelli E, Zannoni GF, Gessi M, Scambia G: Expression of cyclooxygenase-2 (COX-2), receptors for estrogen (ER), and progesterone (PR), p53, ki67, and neu protein in endometrial cancer. Gynecol Oncol. 2005, 98 (3): 383-389. 10.1016/j.ygyno.2005.04.024.CrossRefPubMed
48.
Lazennec G, Bresson D, Lucas A, Chauveau C, Vignon F: ER beta inhibits proliferation and invasion of breast cancer cells. Endocrinology. 2001, 142 (9): 4120-4130. 10.1210/en.142.9.4120.PubMedPubMedCentral
49.
Palmieri C, Lam EW, Mansi J, MacDonald C, Shousha S, Madden P, Omoto Y, Sunters A, Warner M, Gustafsson JA, et al: The expression of ER beta cx in human breast cancer and the relationship to endocrine therapy and survival. Clin Cancer Res. 2004, 10 (7): 2421-2428. 10.1158/1078-0432.CCR-03-0215.CrossRefPubMed
50.
Miller WR, Anderson TJ, Dixon JM, Saunders PT: Oestrogen receptor beta and neoadjuvant therapy with tamoxifen: prediction of response and effects of treatment. Br J Cancer. 2006, 94 (9): 1333-1338. 10.1038/sj.bjc.6603082.CrossRefPubMedPubMedCentral
51.
Murphy LC, Peng B, Lewis A, Davie JR, Leygue E, Kemp A, Ung K, Vendetti M, Shiu R: Inducible upregulation of oestrogen receptor-beta1 affects oestrogen and tamoxifen responsiveness in MCF7 human breast cancer cells. J Mol Endocrinol. 2005, 34 (2): 553-566. 10.1677/jme.1.01688.CrossRefPubMed
52.
Poola I, Abraham J, Baldwin K, Saunders A, Bhatnagar R: Estrogen receptors beta4 and beta5 are full length functionally distinct ERbeta isoforms: cloning from human ovary and functional characterization. Endocrine. 2005, 27 (3): 227-238. 10.1385/ENDO:27:3:227.CrossRefPubMed
53.
Davies MP, O'Neill PA, Innes H, Sibson DR, Prime W, Holcombe C, Foster CS: Correlation of mRNA for oestrogen receptor beta splice variants ER{beta}1, ER{beta}2/ER{beta}cx and ER{beta}5 with outcome in endocrine-treated breast cancer. J Mol Endocrinol. 2004, 33 (3): 773-782. 10.1677/jme.1.01574.CrossRefPubMed
54.
Flototto T, Niederacher D, Hohmann D, Heimerzheim T, Dall P, Djahansouzi S, Bender HG, Hanstein B: Molecular mechanism of estrogen receptor (ER)alpha-specific, estradiol-dependent expression of the progesterone receptor (PR) B-isoform. J Steroid Biochem Mol Biol. 2004, 88 (2): 131-142. 10.1016/j.jsbmb.2003.11.004.CrossRefPubMed
55.
Paech K, Webb P, Kuiper GG, Nilsson S, Gustafsson J, Kushner PJ, Scanlan TS: Differential ligand activation of estrogen receptors ERalpha and ERbeta at AP1 sites. Science. 1997, 277 (5331): 1508-1510. 10.1126/science.277.5331.1508.CrossRefPubMed
56.
van Leeuwen FE, Benraadt J, Coebergh JW, Kiemeney LA, Gimbrere CH, Otter R, Schouten LJ, Damhuis RA, Bontenbal M, Diepenhorst FW, et al: Risk of endometrial cancer after tamoxifen treatment of breast cancer. Lancet. 1994, 343 (8895): 448-452. 10.1016/S0140-6736(94)92692-1.CrossRefPubMed
57.
Gielen SC, Kuhne LC, Ewing PC, Blok LJ, Burger CW: Tamoxifen treatment for breast cancer enforces a distinct gene-expression profile on the human endometrium: an exploratory study. Endocr Relat Cancer. 2005, 12 (4): 1037-1049. 10.1677/erc.1.01046.CrossRefPubMed
58.
Attar E, Tokunaga H, Imir G, Yilmaz MB, Redwine D, Putman M, Gurates B, Attar R, Yaegashi N, Hales DB, et al: Prostaglandin E2 via steroidogenic factor-1 coordinately regulates transcription of steroidogenic genes necessary for estrogen synthesis in endometriosis. J Clin Endocrinol Metab. 2009, 94 (2): 623-631. 10.1210/jc.2008-1180.CrossRefPubMed
59.
Kos M, Reid G, Denger S, Gannon F: Minireview: genomic organization of the human ERalpha gene promoter region. Mol Endocrinol. 2001, 15 (12): 2057-2063. 10.1210/me.15.12.2057.PubMed
60.
Saunders PTK, Millar MR, Williams K, Macpherson S, Harkiss D, Anderson RA, Orr B, Groome NP, Scobie G, Fraser HM: Differential expression of estrogen receptor-alpha and -beta and androgen receptor in the ovaries of marmosets and humans. Biol Reprod. 2000, 63 (4): 1098-1105. 10.1095/biolreprod63.4.1098.CrossRefPubMed
61.
Wong NA, Malcomson RD, Jodrell DI, Groome NP, Harrison DJ, Saunders PT: ERbeta isoform expression in colorectal carcinoma: an in vivo and in vitro study of clinicopathological and molecular correlates. J Pathol. 2005, 207: 53-60. 10.1002/path.1807.CrossRefPubMed
Metadata
Title
Expression of oestrogen receptors, ERα, ERβ, and ERβ variants, in endometrial cancers and evidence that prostaglandin F may play a role in regulating expression of ERα
Authors
Frances Collins
Sheila MacPherson
Pamela Brown
Vincent Bombail
Alistair RW Williams
Richard A Anderson
Henry N Jabbour
Philippa TK Saunders
Publication date
01-12-2009
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2009
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-9-330

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