Increased gene expression of CRTC2 in Ectopic and Eutopic Endometrium of Women with Endometriosis

Background: Endometriosis is an estrogen-dependent disease in women of reproductive age and characterized by the growth of endometrial-like tissues outside the uterine cavity. Aberrant expression of enzymes involved in the biosynthesis of estro-gen, steroidogenic acute regulatory protein (StAR) and aro-matase, have been reported in the endometrium of women with endometriosis. Prostaglandin E2 (PGE2) is a potent inducer of StAR and aromatase expression which impresses its effect via activation of protein kinase A (PKA) and nuclear translocation of cAMP response element binding protein (CREB)-regulat-ed transcription coactivator 2 (CRTC2). PKA phosphorylates CREB which allows it to bind to a CRE site on the promoter re-gions of target genes. In parallel with it, translocation of CRTC2 enhanced its association with CREB to form a transcription complex. CRTC2 belongs to the CREB-regulated transcription coactivator (CRTC) family and enhances CREB transcriptional activity by associating with the leucine zipper DNA-binding region of it. It has been reported that CRTC2 up-regulated the aromatase expression. In addition, CREB/CRTC2 complex di-rectly regulates the expression of a number of critical genes in-volved in cellular proliferation and apoptosis. Previously, we showed overexpression of CREB in ectopic endometrial tissues of women with endometriosis. The aim of this study was to in-vestigate the gene expression profile of CRTC2 in endometrial tissues of women with endometriosis in comparison to controls. Materials and Methods: In this study, 10 normal women (who had no evidence of endometriosis through laparoscopy) and 10 women with endometriosis were enrolled. Ectopic biopsies from endometriosis women were obtained through laparoscopy while control endometrial samples (as a control group) and eutopic samples were collected via pipelle. After endometrial tissues collection, RNA extraction, and cDNA synthesis were done. Real-time PCR technique used for investigating the gene expression profile of CRTC2. Gene expression data were ana-lyzed using one way ANOVA.Results: Gene expression level of CRTC2 was higher in ec-topic and eutopic endometrium of women with endometriosis in comparison to control group.Conclusion: The increased gene expression of CRTC2 in ec-topic and eutopic endometrium of women with endometriosis may contribute to the pathogenesis of endometriosis through its regulatory role on target gene expression.

کلیدواژه ها:

Endometriosis ، CREB ، CRTC2 ، eutopic ، ectopic