title: Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer.
abstract: 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.
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsushima
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Taisuke
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Fumitake
authors.initials: F
authors.lastname: Ito
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Yamamoto
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Akiyama
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Kokabu
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Yoriki
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Umemura
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Akashi
authors.affiliation: Department of Obstetrics and Gynecology, Kyoto Prefectural University of Medicine, Graduate School of Medical Science, Kajii-cho, Kamigyo-ku, Kyoto, Japan.
authors.forename: Jo
authors.initials: J
authors.lastname: Kitawaki
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D016889:Endometrial Neoplasms / Q000378:metabolism / Q000473:pathology*; D005260:Female; D055785:Gene Knockdown Techniques; D064593:Heterografts; D006801:Humans; D051379:Mice; D009389:Neovascularization, Pathologic / Q000378:metabolism; D011960:Receptors, Estrogen / Q000032:analysis / Q000096:biosynthesis*; D000097983:ERRalpha Estrogen-Related Receptor
chemical_list: D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D000097983:ERRalpha Estrogen-Related Receptor
keywords: ERRα; VEGF; apoptosis; cell cycle arrest; uterine endometrial cancer