ERβ shifts from mitochondria to nucleus during estrogen-induced neoplastic transformation of human breast epithelial cells and is involved in estrogen-induced synthesis of mitochondrial respiratory chain proteins
ERβ shifts from mitochondria to nucleus during estrogen-induced neoplastic transformation of human breast epithelial cells and is involved in estrogen-induced synthesis of mitochondrial respiratory chain proteins
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DOI：
10.1016/j.bbamcr.2007.05.008
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发表时间：
2007-12-01
影响因子：
5.1
通讯作者：
Russo, Jose
中科院分区：
文献类型：
--
作者：
Chen, Jin-Qiang;Russo, Patricia A.;Russo, Jose
雌激素受体(ER) α (ER α)和β (ER β)均存在于细胞核、质膜和线粒体中，介导雌激素的不同生理作用。已经观察到，在一些癌细胞中，内质网的相对亚细胞定位发生了改变。我们已经证明，具有ER α阴性和ER β阳性的人乳腺上皮细胞（HBEC） MCF-10F细胞在体外被17 β -雌二醇（E-2）转化，在严重联合免疫缺陷小鼠中产生高度侵袭性的致瘤细胞。e -2转化的MCF-10F （trMCF）细胞表现出导管生成、侵袭性（bsMCF）和致瘤性（caMCF）表型的进行性丧失。通过共聚焦荧光显微镜和电镜对ER β的免疫定位发现，ER β主要定位于MCF-10F和trMCF细胞的线粒体中。用ER β特异性小干扰RNA （siRNA-ER β）沉默ER β表达可显著减少MCF-10F细胞的核和线粒体ER β。ER β从MCF-10F和trMCF细胞的线粒体转移到bsMCF细胞的细胞核，在caMCF细胞中主要变成核。此外，我们证明了MCF-10F细胞中的线粒体ER β参与了e -2诱导的线粒体DNA （mtDNA）编码呼吸链（MRC）蛋白的表达。这是首次报道ERA的亚细胞定位变化与e -2诱导的HBEC转化的各个阶段以及线粒体W在介导e -2诱导的MRC蛋白合成中的功能作用相关。我们的发现为ERA在人类乳腺癌中的潜在作用之一提供了新的见解。(c) 2007 Elsevier B.V.版权所有
Both estrogen receptors (ER) alpha (ER alpha) and beta (ER beta) are localized in the nucleus, plasma membrane, and mitochondria, where they mediate the different physiological effects of estrogens. It has been observed that the relative subcellular localization of ERs is altered in several cancer cells. We have demonstrated that MCF-10F cells, the immortal and non-tumorigenic human breast epithelial cells (HBEC) that are ER alpha-negative and ER beta-positive, are transformed in vitro by 17 beta-estradiol (E-2), generating highly invasive cells that are tumorigenic in severe combined immunodeficient mice. E-2-transformed MCF-10F (trMCF) cells exhibit progressive loss of ductulogenesis, invasive (bsMCF) and tumorigenic (caMCF) phenotypes. Immunolocalization of ER beta by confocal fluorescent microscopy and electron microscopy revealed that ER beta is predominantly localized in mitochondria of MCF-10F and trMCF cells. Silencing ER beta expression with ER beta-specific small interference RNA (siRNA-ER beta) markedly diminishes both nuclear and mitochondrial ER beta in MCF-10F cells. The ER beta shifts from its predominant localization in the mitochondria of MCF-10F and trMCF cells to the nucleus of bsMCF cells, becoming predominantly nuclear in caMCF cells. Furthermore, we demonstrated that the mitochondrial ER beta in MCF-10F cells is involved in E-2-induced expression of mitochondrial DNA (mtDNA)-encoded respiratory chain (MRC) proteins. This is the first report of an association of changes in the subcellular localization of ERA with various stages of E-2-induced transformation of HBEC and a functional role of mitochondrial W in mediating E-2-induced MRC protein synthesis. Our findings provide a new insight into one of the potential roles of ERA in human breast cancer. (c) 2007 Elsevier B.V. All rights reserved.