Analyses of tissue-specific action of SERMs using real-time imaging techniques

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ER_α在雌二醇(E_2)存在的情况下形成核内病灶，但在乳腺癌细胞系中ER_2被移位到核仁中。在其他组织的细胞中没有观察到这种现象。免疫荧光染色显示，在RLX存在的情况下，内源性ERα也被转移到核仁内。突变分析表明，ERα的螺旋12对于ERα的核仁易位是必不可少的。这些结果表明，ERα移位到核仁中是RLX特异性的，是RLX诱导的乳腺细胞生长抑制的关键事件。

To clarify the molecular mechanism underlying the tissue specificity of SERMs, we examined the intracellular localization of ERα using a green fluorescent protein (GFP)-tagged protein in culture cells from various tissues. Although ERα formed intranuclear foci in the presence of estradiol (E2), RLX translocated ER_into the nucleoli in breast cancer cell lines. This phenomenon was not observed in cells from other tissues. Immunofluorescence staining revealed that endogenous ERα was also translocated into the nucleoli in the presence of RLX. Mutation analyses demonstrate that helix 12 of ERα is essential to the nucleolar translocation of ERα. These results suggest that translocation of ERα into the nucleoli is RLX-specific and is a key event for RLX-induced growth repression of mammary gland cells.