Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan; Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
Environ Pollut. 2011 Jan;159(1):212-218. doi: 10.1016/j.envpol.2010.09.004. Epub 2010 Sep 27.
Bisphenol A (BPA) has been considered as an endocrine disruptor due to its ability to interact with estrogen receptors (ERs). While G protein-coupled receptor 30 (GPR30) is a novel estrogen receptor, its role in BPA-induced activation of Erk1/2 remains unknown. Human breast cancer cell lines, MCF-7, MDA-MB-231 and SKBR3, were used as experimental models to discriminate between ERs-dependent, putative ERs-independent and/or GPR30-associated effects. BPA induced a rapid activation of Erk1/2 in both ERα/β-positive and negative breast cancer cells, and this effect was not blocked with an ER antagonist, ICI 182,780. A small interfering RNA assay revealed that the expression of GPR30 was necessary for BPA-induced activation of Erk1/2 and transcriptional regulation of c-fos. In addition, BPA regulates the expression of c-fos likely through an AP1-mediated pathway. As a conclusion, GPR30 plays an important role in the BPA-induced activation of Erk1/2 in a manner distinguishable from that in ERα-mediated signaling.
双酚 A（BPA）因其能够与雌激素受体（ERs）相互作用而被认为是一种内分泌干扰物。虽然 G 蛋白偶联受体 30（GPR30）是一种新型的雌激素受体，但它在 BPA 诱导的 Erk1/2 激活中的作用尚不清楚。人乳腺癌细胞系 MCF-7、MDA-MB-231 和 SKBR3 被用作实验模型，以区分 ER 依赖性、假定的 ER 非依赖性和/或 GPR30 相关效应。BPA 诱导 ERα/β 阳性和阴性乳腺癌细胞中 Erk1/2 的快速激活，而这种效应不能被 ER 拮抗剂 ICI 182,780 阻断。小干扰 RNA 测定表明，GPR30 的表达对于 BPA 诱导的 Erk1/2 激活和 c-fos 的转录调节是必要的。此外，BPA 可能通过 AP1 介导的途径调节 c-fos 的表达。总之，GPR30 在 BPA 诱导的 Erk1/2 激活中发挥重要作用，其方式与 ERα 介导的信号传导不同。
