Enhanced epithelial to mesenchymal transition (EMT) and upregulated MYC in ectopic lesions contribute independently to endometriosis

Reproductive Biology and Endocrinology

Research

Katharina Proestling¹  Nadine Nirtl¹  Erika Marton¹  Susanne Gamperl¹  Rene Wenzl¹  Gülen Yerlikaya¹  Berthold Streubel¹  Heinrich Husslein²  Peter Birner³ 

[1] Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria;Department of Obstetrics and Gynecology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria;Department of Obstetrics and Gynecology, St. Michael’s Hospital, University of Toronto, 30 Bond street, M5B 1 W8, Toronto, Ontorio, Canada;Department of Pathology, Medical University of Vienna, Waehringer Guertel 18-20, 1090, Vienna, Austria;

关键词: Endometriosis;    MYC;    TWIST1;    SNAIL;    SLUG;    EMT;   

DOI  :  10.1186/s12958-015-0063-7

 received in 2015-01-29, accepted in 2015-06-09,  发布年份 2015

来源: Springer

【 摘 要 】

BackgroundEpithelial to mesenchymal transition (EMT) is a process in which epithelial cells lose polarity and cell-to-cell contacts and acquire the migratory and invasive abilities of mesenchymal cells. These abilities are thought to be prerequisites for the establishment of endometriotic lesions. A hallmark of EMT is the functional loss of E-cadherin (CDH1) expression in epithelial cells. TWIST1, a transcription factor that represses E-cadherin transcription, is among the EMT inducers. SNAIL, a zinc-finger transcription factor, and its close relative SLUG have similar properties to TWIST1 and are thus also EMT inducers. MYC, which is upregulated by estrogens in the uterus by an estrogen response cis-acting element (ERE) in its promoter, is associated with proliferation in endometriosis. The role of EMT and proliferation in the pathogenesis of endometriosis was evaluated by analyzing TWIST1, CDH1 and MYC expression.MethodsCDH1, TWIST1, SNAIL and SLUG mRNA expression was analyzed by qRT-PCR from 47 controls and 74 patients with endometriosis. Approximately 42 ectopic and 62 eutopic endometrial tissues, of which 30 were matched samples, were collected during the same surgical procedure. We evaluated TWIST1 and MYC protein expression by immunohistochemistry (IHC) in the epithelial and stromal tissue of 69 eutopic and 90 ectopic endometrium samples, of which 49 matched samples were analyzed from the same patient. Concordant expression of TWIST1/SNAIL/SLUG and CDH1 but also of TWIST1 and MYC was analyzed.ResultsWe found that TWIST1, SNAIL and SLUG are overexpressed (p < 0.001, p = 0.016 and p < 0.001) in endometriosis, while CDH1 expression was concordantly reduced in these samples (p < 0.001). Similar to TWIST1, the epithelial expression of MYC was also significantly enhanced in ectopic endometrium compared to eutopic tissues (p = 0.008). We found exclusive expression of either TWIST1 or MYC in the same samples (p = 0.003).ConclusionsEpithelial TWIST1 is overexpressed in endometriosis and may contribute to the formation of endometriotic lesions by inducing epithelial to mesenchymal transition, as CDH1 was reduced in ectopic lesions. We found exclusive expression of either TWIST1 or MYC in the same samples, indicating that EMT and proliferation contribute independently of each other to the formation of endometriotic lesions.

【 授权许可】

Unknown   
© Proestling et al. 2015. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.