Besides genetic disorders, dysregulation of epigenetic machinery has been proved to play a crucial role in human carcinogenesis, and the histone methylation/demethylation process has been considered as one of key regulators for this event. However, the roles of these alterations in cancer progression have not been well characterized in endometrial cancer. The aim of this study is to elucidate that one of methyltransferases, enhancer of zeste homolog 2 (EZH2) is a novel target of anti-cancer therapy in endometrial cancer.
We demonstrate that EZH2 plays pivotal roles in human endometrial cancer. To confirm these roles, we performed the expression profile of EZH2 in 11 endometrial cancer cell lines and 50 clinical endometrial cancer specimens, under informed consent and approval of our ethics committee. In addition, we performed the functional analysis of
EZH2 using endometrial cancer cell lines. The expression Quantitative real-time PCR revealed that EZH2 is aberrantly overexpressed in endometrial cancer cell lines and clinical samples compared with immortalized endometrial cell line and normal endometrial tissues (P<0.05). The reduction of EZH2 expression by small interfering RNAS resulted in suppression of growth of cancer cells and caused apoptotic cell death in endometrial cancer cell lines.
Our results suggest that dysregulation of EZH2 plays an important role in the growth regulation of endometrial cancer cells, and further functional studies may affirm the importance of EZH2 as a promising therapeutic target for endometrial cancer.
Citation Format: SHINYA OKI, KENBUN SONE, KATSUTOSHI ODA, AKIRA NISHIJIMA, MAKOTO TAKEUCHI, CHUWA AGAPITI, KAYO ASADA, CHINAMI MAKII, KEI KAWANA, YUTAKA OSUGA, TOMOYUKI FUJII. The histone methyltransferase EZH2 is a novel target of anticancer therapy in endometrial cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 969A.