Analysis and treatment-application of novel nongenomic action of estrogen receptor mediated by protein deacetylation

本研究的目的是分析雌激素受体的非基因组作用在乳腺癌和骨质疏松症等疾病中的作用，并与雌激素作用有关。雌激素受体的非基因组作用是新近阐明的雌激素受体的作用，不能用雌激素受体作为配体依赖的转录因子的作用来解释。结果表明，非基因组作用是由细胞膜上的雌激素受体而不是细胞核内的雌激素受体介导的。在这项研究中，我们通过稳定表达膜定位雌激素受体的乳腺癌细胞，证明了一些依赖于膜定位雌激素受体的基因。我们还建立了同时表达荧光素酶和膜定位雌激素受体的乳腺癌细胞株，为评价雌激素受体的非基因组作用对转移潜能的影响提供了有用的工具。在本研究中，我们还准备了表达膜定位雌激素受体的成骨细胞系，以评价雌激素受体的非基因组作用对骨质疏松的影响。

The aim of this study is to analyze the role of nongenomic action of estrogen receptor in the disease such as breast cancer and osteoporosis, which has relationship with estrogen action. Nongenomic action is newly clarified action of estrogen receptor, which cannot be explained by the formerly-known action of estrogen receptor as a ligand-dependent transcription factor. It was shown that nongenomic action was mediated by estrogen receptor at the plasma membrane instead of estrogen receptor in the nucleus. In this study we demonstrated some genes dependent on the membrane-localizing estrange receptor by using breast cancer cells stably expressing membrane-localizing estrogen receptor. We also established breast cancer cell line expressing both luciferase and membrane-localizing estrogen receptor, which can be a useful tool for evaluating effect of nongenomic action of estrogen receptor on metastatic potential. In this study, we are also preparing osteoblastic cell line expressing membrane-localizing estrogen receptor for evaluating effect of nongenomic action of estrogen receptor on osteoporosis.