Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer
Estrogen-related receptor γ modulates cell proliferation and estrogen signaling in breast cancer
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DOI：
10.1016/j.jsbmb.2010.09.002
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Ijichi, Nobuhiro;Shigekawa, Takashi;Inoue, Satoshi
乳腺癌主要是一种激素依赖性肿瘤，可通过雌激素和黄体酮等类固醇激素的状态进行调节。雌激素相关受体（estrogen -related receptor, ERRs）是与雌激素受体（estrogen - receptor， ER）关系最为密切的孤儿核受体，近年来研究ERRs与雌激素受体（estrogen - receptor， ER）的相互作用在乳腺癌中的作用受到了广泛关注。在本研究中，我们通过免疫组织化学分析（n =110）研究了乳腺癌根治术后ERR γ在人浸润性乳腺癌中的表达。87例（79%）检测到ERR γ的核免疫反应性，并倾向于与淋巴结状态相关。未观察到与其他临床病理特征，包括雌激素和孕激素受体的表达水平有显著关联。在MCF-7乳腺癌细胞中，我们证实雌激素对ERR γ mRNA的剂量依赖性上调，而ICI 182780治疗可消除雌激素对ERR γ mRNA的上调。我们还证明外源性转染ERR γ增加MCF-7细胞增殖。此外，ERR γ增强了MCF-7细胞中雌激素反应元件（ERE）驱动的转录。在2931个细胞中，ERR γ也可以刺激有或没有ER α的ere介导的转录。这些结果表明ERR γ在乳腺癌细胞中作为雌激素信号的调节剂起着重要作用。(C) 2010 Elsevier Ltd.版权所有。
Breast cancer is primarily a hormone-dependent tumor that can be regulated by status of steroid hormones including estrogen and progesterone. Estrogen-related receptors (ERRs) are orphan nuclear receptors most closely related to estrogen receptor (ER) and much attention has been recently paid to the functions of ERRs in breast cancer in terms of the interactions with ER. In the present study, we investigated the expression of ERR gamma in human invasive breast cancers by immunohistochemical analysis (n =110) obtained by radical mastectomy. Nuclear immunoreactivity of ERR gamma was detected in 87 cases (79%) and tended to correlate with the lymph node status. No significant associations were observed with other clinicopathological characteristics, including the expression levels of both estrogen and progesterone receptors. In MCF-7 breast cancer cells, we demonstrated that ERR gamma mRNA was up-regulated dose-dependently by estrogen, and that this up-regulation of ERR gamma mRNA by estrogen was abolished by ICI 182,780 treatment. We also demonstrated that exogenously transfected ERR gamma increased MCF-7 cell proliferation. Furthermore, ERR gamma enhanced estrogen response element (ERE)-driven transcription in MCF-7 cells. In 2931 cells, ERR gamma could also stimulate ERE-mediated transcription with or without ER alpha. These results suggest that ERR gamma plays an important role as a modulator of estrogen signaling in breast cancer cells. (C) 2010 Elsevier Ltd. All rights reserved.