{"paper_id":"c11fc2fd-eff1-4798-b3b5-7d84f1d435ae","body_text":"Abstract\nPurpose\nThe nuclear hormone receptor estrogen receptor α (ERα) is pivotal for numerous processes in the cell. As a transcription factor, it regulates eukaryotic gene expression and affects cellular proliferation and differentiation in target tissues. Moreover, ERα is known for its influence on various gynecological diseases and carcinogenesis. Since its expression is often altered in diseased tissues and this alteration was found to be caused by hypermethylation of the ESR1 promotor region in cancer, including breast and colorectal cancer, the aim of this study is to elucidate if the expression of ERα is also regulated epigenetically in endometriosis and endometrial cancer.\nMethods\nUsing real-time methylation-specific PCR (rt-MSP), we examined endometrial and endometriotic tissues as well as five endometrial cancer cell lines and compared the methylation status with the actual expression of ERα.\nResults\nThe results of our study indicate that, though its expression is altered in endometrial and endometriotic tissue, ERα is not regulated by methylation of the promotor region in endometriosis. In contrast, three of the five endometrial cancer cell lines are methylated in the promotor region of ESR1.\nConclusions\nThus, further investigation of the connection between ERα and endometrial cancer will be the next step.\nSimilar content being viewed by others\nChange history\n08 June 2018\nIn the original publication of the article, the name of first author was misspelled. The correct name has been copied below:\nReferences\nAli SH, O’donnell AL, Mohamed S et al (2004) Overexpression of estrogen receptor-alpha in the endometrial carcinoma cell line Ishikawa: inhibition of growth and angiogenic factors. Gynecol Oncol 95:637–645\nBerger U, Mcclelland RA, Wilson P et al (1991) Immunocytochemical determination of estrogen receptor, progesterone receptor, and 1,25-dihydroxyvitamin D3 receptor in breast cancer and relationship to prognosis. Can Res 51:239–244\nBloski T, Pierson R (2008) Endometriosis and chronic pelvic pain: unraveling the mystery behind this complex condition. Nurs Women’s Health 12:382–395\nBopp B, Shoupe D (1993) Luteal phase defects. J Reprod Med 38:348–356\nCunha-Filho JS, Gross JL, Bastos De Souza CA et al (2003) Physiopathological aspects of corpus luteum defect in infertile patients with mild/minimal endometriosis. J Assist Reprod Genet 20:117–121\nEads CA, Lord RV, Kurumboor SK et al (2000) Fields of aberrant CpG island hypermethylation in Barrett’s esophagus and associated adenocarcinoma. Can Res 60:5021–5026\nEeckhoute J, Keeton EK, Lupien M et al (2007) Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer. Can Res 67:6477–6483\nElledge RM, Green S, Pugh R et al (2000) Estrogen receptor (ER) and progesterone receptor (PgR), by ligand-binding assay compared with ER, PgR and pS2, by immuno-histochemistry in predicting response to tamoxifen in metastatic breast cancer: a Southwest Oncology Group Study. Int J Cancer 89:111–117\nEngemise SL, Willets JM, Taylor AH et al (2011) Changes in glandular and stromal estrogen and progesterone receptor isoform expression in eutopic and ectopic endometrium following treatment with the levonorgestrel-releasing intrauterine system. Eur J Obstet Gynecol Reprod Biol 157:101–106\nEsteller M, Corn PG, Baylin SB et al (2001) A gene hypermethylation profile of human cancer. Can Res 61:3225–3229\nHarder J, Engelstaedter V, Usadel H et al (2009) CpG-island methylation of the ER promoter in colorectal cancer: analysis of micrometastases in lymph nodes from UICC stage I and II patients. Br J Cancer 100:360–365\nHolmes KA, Song JS, Liu XS et al (2008) Nk3–1 and LEF-1 function as transcriptional inhibitors of estrogen receptor activity. Can Res 68:7380–7385\nHolst F, Hoivik EA, Gibson WJ et al (2016) Recurrent hormone-binding domain truncated ESR1 amplifications in primary endometrial cancers suggest their implication in hormone independent growth. Sci Rep 6:25521\nHua S, Kittler R, White KP (2009) Genomic antagonism between retinoic acid and estrogen signaling in breast cancer. Cell 137:1259–1271\nHurtado A, Holmes KA, Geistlinger TR et al (2008) Regulation of ERBB2 by oestrogen receptor-PAX2 determines response to tamoxifen. Nature 456:663–666\nIssa JP, Ottaviano YL, Celano P et al (1994) Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet 7:536–540\nIssa JP, Zehnbauer BA, Civin CI et al (1996) The estrogen receptor CpG island is methylated in most hematopoietic neoplasms. Can Res 56:973–977\nJemal A, Bray F, Center MM et al (2011) Global cancer statistics. CA Cancer J Clin 61:69–90\nJongen V, Briet J, De Jong R et al (2009) 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 112:537–542\nKanwal R, Gupta S (2012) Epigenetic modifications in cancer. Clin Genet 81:303–311\nKokka F, Brockbank E, Oram D et al (2010) Hormonal therapy in advanced or recurrent endometrial cancer. Cochrane Database Syst Rev. doi:10.1002/14651858.CD007926.pub2\nLapidus RG, Ferguson AT, Ottaviano YL et al (1996) Methylation of estrogen and progesterone receptor gene 5′ CpG islands correlates with lack of estrogen and progesterone receptor gene expression in breast tumors. Clin Cancer Res Off J Am Assoc Cancer Res 2:805–810\nLapidus RG, Nass SJ, Butash KA et al (1998) Mapping of ER gene CpG island methylation-specific polymerase chain reaction. Can Res 58:2515–2519\nLapidus RG, Nass SJ, Davidson NE (1998) The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mamm Gland Biol Neoplasia 3:85–94\nLi Q, Seo JH, Stranger B et al (2013) Integrative eQTL-based analyses reveal the biology of breast cancer risk loci. Cell 152:633–641\nLiu X, Shi H (2015) Regulation of estrogen receptor α expression in the hypothalamus by sex steroids: implication in the regulation of energy homeostasis. Int J Endocrinol 2015:949085\nMatorras R, Rodriguez F, Perez C et al (1996) Infertile women with and without endometriosis: a case control study of luteal phase and other infertility conditions. Acta Obstet Gynecol Scand 75:826–831\nMoeloek FA, Moegny E (1993) Endometriosis and luteal phase defect. Asia Ocean J Obstetr Gynaecol 19:171–176\nPandya KJ, Yeap BY, Weiner LM et al (2001) Megestrol and tamoxifen in patients with advanced endometrial cancer: an Eastern Cooperative Oncology Group Study (E4882). Am J Clin Oncol 24:43–46\nRendina GM, Donadio C, Fabri M et al (1984) Tamoxifen and medroxyprogesterone therapy for advanced endometrial carcinoma. Eur J Obstet Gynecol Reprod Biol 17:285–291\nRogers PA, D’hooghe TM, Fazleabas A et al (2009) Priorities for endometriosis research: recommendations from an international consensus workshop. Reprod Sci (Thousand Oaks, Calif) 16:335–346\nRoss-Innes CS, Stark R, Holmes KA et al (2010) Cooperative interaction between retinoic acid receptor-alpha and estrogen receptor in breast cancer. Genes Dev 24:171–182\nThigpen T, Brady MF, Homesley HD et al (2001) Tamoxifen in the treatment of advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group study. J Clin Oncol 19:364–367\nYue W, Yager JD, Wang JP et al (2013) Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78:161–170\nAuthor information\nAuthors and Affiliations\nContributions\nVT: Performed the experiments, wrote the first draft of the manuscript. MR: Performed the experiments, supervised the methodology. SH: Performed the experiments, supervised the methodology. VK: Developed the Methodology of the methylation analyses. SM: Organized and Supervised Funding and final manuscript preparation. UJ: Supervised the Methodology and the final draft of the manuscript. VvS: Development of the project idea, principal supervision of the investigators.\nCorresponding author\nEthics declarations\nFunding\nThis study was funded by the Medical Faculty of the Ludwig Maximilians University of Munich.\nConflict of interest\nAll authors declare that they have no conflict of interest.\nEthical approval\nAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\nInformed consent\nInformed consent was obtained from all individual participants included in the study.\nRights and permissions\nAbout this article\nCite this article\nToderow, V., Rahmeh, M., Hofmann, S. et al. Promotor analysis of ESR1 in endometrial cancer cell lines, endometrial and endometriotic tissue. Arch Gynecol Obstet 296, 269–276 (2017). https://doi.org/10.1007/s00404-017-4405-x\nReceived:\nAccepted:\nPublished:\nIssue date:\nDOI: https://doi.org/10.1007/s00404-017-4405-x","source_license":"CC0","license_restricted":false}