Promotor analysis of ESR1 in endometrial cancer cell lines, endometrial and endometriotic tissue

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This study examined if ERα expression in endometriosis and endometrial cancer is regulated by ESR1 promoter methylation, finding it is not in endometriosis but is in three of five cancer cell lines.

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This study examined whether estrogen receptor alpha (ERα), encoded by ESR1, is epigenetically regulated through methylation of its promoter in endometrial and endometriotic tissues, using real-time methylation-specific PCR and comparing methylation status with ERα expression in five endometrial cancer cell lines. The authors reported that although ERα expression is altered in endometrial and endometriotic tissue, ERα was not regulated by ESR1 promoter methylation in endometriosis. In contrast, three of five endometrial cancer cell lines showed ESR1 promoter methylation. This paper is centrally about endometriosis — it tests whether ESR1 promoter methylation accounts for ERα expression changes in endometriotic tissue.

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Abstract

Purpose The 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.

Methods

Using 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.

Results

The 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.

Conclusions

Thus, further investigation of the connection between ERα and endometrial cancer will be the next step. Similar content being viewed by others Change history 08 June 2018 In the original publication of the article, the name of first author was misspelled. The correct name has been copied below:

References

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Reprod Sci (Thousand Oaks, Calif) 16:335–346 Ross-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 Thigpen 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 Yue W, Yager JD, Wang JP et al (2013) Estrogen receptor-dependent and independent mechanisms of breast cancer carcinogenesis. Steroids 78:161–170 Author information Authors and Affiliations Contributions VT: 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. Corresponding author Ethics declarations Funding This study was funded by the Medical Faculty of the Ludwig Maximilians University of Munich. Conflict of interest All authors declare that they have no conflict of interest. Ethical approval All 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. Informed consent Informed consent was obtained from all individual participants included in the study. Rights and permissions About this article Cite this article Toderow, 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 Received: Accepted: Published: Issue date: DOI: https://doi.org/10.1007/s00404-017-4405-x

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Condition tags

mesh:D004715

MeSH descriptors

Endometrial Neoplasms Endometriosis Estrogen Receptor alpha Promoter Regions, Genetic Cell Line, Tumor DNA Methylation Endometrial Neoplasms Endometriosis Endometriosis Endometrium Endometrium Estrogen Receptor alpha Estrogen Receptor alpha Female Gene Expression Regulation Humans Transcription, Genetic

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