Bisphenol A induces a rapid activation of Erk1/2 through GPR30 in human breast cancer cells

Environ Pollut. 2011 Jan;159(1):212-218. doi: 10.1016/j.envpol.2010.09.004. Epub 2010 Sep 27.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Blotting, Western
  • Breast Neoplasms / enzymology*
  • Cell Line, Tumor
  • Enzyme Activation / drug effects
  • Female
  • Humans
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism*
  • Phenols / toxicity*
  • Proto-Oncogene Proteins c-fos / genetics
  • Proto-Oncogene Proteins c-fos / metabolism
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • Benzhydryl Compounds
  • GPER1 protein, human
  • Phenols
  • Proto-Oncogene Proteins c-fos
  • Receptors, Estrogen
  • Receptors, G-Protein-Coupled
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3
  • bisphenol A