E2弱化双酚A雌激素活性机制

Mechanisms of E2 weakening effects on BPA’s estrogenicity

摘要:

前期研究发现天然雌激素E2可以弱化一种常见雌激素类污染物双酚A的活性,为探讨这一现象的机制,利用人体乳腺癌细胞MCF7,从细胞周期、雌激素受体途径、MAPKs信号途径进行实验．结果表明:E2可诱导DNA合成期细胞显著增高,抑制受体蛋白表达,提高ERK蛋白的表达,进而激活多种转录因子;双酚A显著抑制受体蛋白表达,对MAPKs信号通路基本没有影响,可同时提高DNA分裂期与间歇期细胞比例;两者联合后活化了受体途径和ERK途径,促进Cfos的转录表达,激活cyclin D1蛋白,增加S期及G2期细胞比例．E2弱化双酚A的可能机制为Cmyc蛋白表达下降．

Abstract:

Previous study showed that natural estrin, 17Estradiol (E2), could weaken the estrogenicity of Bisphenol A (BPA), a common estrin in water resources. In order to learn the potential mechanisms, experiments were performed with human breast cancer cell MCF7 on the cell cycle, estrogen receptor pathway and MAPKs pathway. Results showed that E2 worked through estrogen receptors and ERK pathway, and activated Cmyc gene, Cfos gene, and cyclin D1 protein, and thus increased the S section of the cell cycle. BPA worked mainly through estrogen receptors by activating cyclin D1 protein, and increased the S and G2 sections of the cell cycle. The mixture of BPA and E2 worked through both pathways, activated both Cfos and cyclin D1, and increased both S and G2 sections of the cell cycle. The main mechanism of E2’s weakening on BPA’s estrogenicity might be the decreased expression of Cmyc protein.