Raloxifene induces nucleolar translocation of the estrogen receptor
Raloxifene induces nucleolar translocation of the estrogen receptor
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DOI：
10.1016/j.mce.2010.01.006
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发表时间：
2010-05-05
影响因子：
4.1
通讯作者：
Takayanagi, Ryoichi
中科院分区：
文献类型：
--
作者：
Gushima, Mika;Kawate, Hisaya;Takayanagi, Ryoichi
雷洛昔芬(RLX)是一种选择性雌激素受体调节剂(SERM)，与雌激素受体α(ERα)结合，在某些组织中作为激动剂，在另一些组织中作为拮抗剂。为了阐明SERM的组织特异性的分子机制，我们使用绿色荧光蛋白(GFP)标记的蛋白在不同组织的培养细胞中检测了ERα的细胞内定位。虽然ERα在雌二醇(E-2)存在的情况下形成核内病灶。RLX在乳腺癌细胞系中将ERα转位到核仁中，这一现象在其他组织的细胞中没有观察到。免疫荧光染色显示，在RLX存在的情况下，内源性ERα也被移位到核仁中。突变分析表明，ERα的螺旋12对于ERα的核仁移位是必不可少的。这些结果表明，ERα移位到核仁中是RLX特有的，是RLX诱导的乳腺细胞生长抑制的关键事件(C)2010爱思唯尔爱尔兰有限公司保留所有权利。
Raloxifene (RLX), a selective estrogen receptor modulator (SERM), binds to the estrogen receptor alpha (ER alpha) and acts as an agonist in some tissues, and as an antagonist in others. To clarify the molecular mechanism underlying the tissue specificity of SERMs, we examined the intracellular localization of ER alpha using a green fluorescent protein (GFP)-tagged protein in culture cells from various tissues. Although ER alpha formed intranuclear foci in the presence of estradiol (E-2). RLX translocated ER alpha into the nucleoli in breast cancer cell lines This phenomenon was not observed in cells from other tissues. Immunofluorescence staining revealed that endogenous ER alpha was also translocated into the nucleoli in the presence of RLX Mutation analyses demonstrate that helix 12 of ER alpha is essential to the nucleolar translocation of ER alpha These results suggest that translocation of ER alpha into the nucleoli is RLX-specific and is a key event for RLX-induced growth repression of mammary gland cells (C) 2010 Elsevier Ireland Ltd All rights reserved.