Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells.
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.
Dong
S
S
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.
Terasaka
S
S
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan.
Kiyama
R
R
Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki 305-8566, Japan. Electronic address: kiyama.r@aist.go.jp.
D001559:Benzhydryl Compounds; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000201:enzymology*; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D006801:Humans; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism*; D010636:Phenols / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010636:Phenols; D016760:Proto-Oncogene Proteins c-fos; D011960:Receptors, Estrogen; D043562:Receptors, G-Protein-Coupled; C109584:GPER1 protein, human; C006780:bisphenol A; D000098826:Bisphenol A Compounds