Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer
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Hiroshi Matsushima1, Taisuke Mori1, Fumitake Ito1, Takuro Yamamoto1, Makoto Akiyama1, Tetsuya Kokabu1, Kaori Yoriki1, Shiori Umemura1, Kyoko Akashi1 and Jo Kitawaki1
1 Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan
Taisuke Mori, email:
Keywords: apoptosis, cell cycle arrest, ERRα, VEGF, uterine endometrial cancer
Received: December 24, 2015 Accepted: April 16, 2016 Published: May 03, 2016
Estrogen-related receptor (ERR)α presents structural similarities with estrogen receptor (ER)α. However, it is an orphan receptor not binding to naturally occurring estrogens. This study was designed to investigate the role of ERRα in endometrial cancer progression. Immunohistochemistry analysis on 50 specimens from patients with endometrial cancer showed that ERRα was expressed in all examined tissues and the elevated expression levels of ERRα were associated with advanced clinical stages and serous histological type (p < 0.01 for each). ERRα knockdown with siRNA suppressed angiogenesis via VEGF and cell proliferation in vitro (p < 0.01). Cell cycle and apoptosis assays using flow cytometry and western blot revealed that ERRα knockdown induced cell cycle arrest during the mitotic phase followed by apoptosis initiated by caspase-3. Additionally, ERRα knockdown sensitized cells to paclitaxel. A significant reduction of tumor growth and angiogenesis was also observed in ERRα knockdown xenografts (p < 0.01). These findings indicate that ERRα may serve as a novel molecular target for the treatment of endometrial cancer.
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