Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer.

Anti-tumor effect of estrogen-related receptor alpha knockdown on uterine endometrial cancer.
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DOI:
10.18632/oncotarget.9151
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发表时间:
2016-06-07
期刊:
影响因子:
--
通讯作者:
Kitawaki J
Kitawaki J
中科院分区:
其他
文献类型:
--
作者:
Matsushima H;Mori T;Ito F;Yamamoto T;Akiyama M;Kokabu T;Yoriki K;Umemura S;Akashi K;Kitawaki J

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雌激素相关受体(ERR)α与雌激素受体(ER)α具有结构相似性。然而,它是一种孤儿受体,不与天然存在的雌激素结合。本研究旨在探讨ERR α在子宫内膜癌进展中的作用。50例子宫内膜癌标本的免疫组化结果显示,ERR α在所有被检组织中均有表达,且其表达水平与临床分期、浆液性组织学类型有关(P <0.01)。siRNA敲低ERR α可抑制VEGF介导的血管生成和细胞增殖(p <0.01)。流式细胞术和蛋白质印迹法检测细胞周期和凋亡,结果显示ERR α基因敲低可诱导细胞周期阻滞于有丝分裂期,随后凋亡由caspase-3启动。此外,ERR α敲低使细胞对紫杉醇敏感。在ERR α敲低的异种移植物中也观察到肿瘤生长和血管生成的显著减少(p <0.01)。这些结果表明ERR α可能成为治疗子宫内膜癌的一个新的分子靶点。
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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