Open AccessAnti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer
Author(s) -
Hiroshi Miyata,
Taisuke Mori,
Fumihiko Ito,
Takuro Yamamoto,
Makoto Akiyama,
Tetsuya Kokabu,
Kaori Yoriki,
Satoshi Umemura,
Koichi Akashi,
Jo Kitawaki
Publication year - 2016
Publication title -
oncotarget
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.373
H-Index - 127
ISSN - 1949-2553
DOI - 10.18632/oncotarget.9151
Subject(s) - gene knockdown , cancer research , angiogenesis , estrogen receptor , cell growth , endometrial cancer , apoptosis , progesterone receptor , medicine , biology , cancer , chemistry , breast cancer , biochemistry , genetics
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.