Effect of bisphenol A on the EGFR-STAT3 pathway in MCF-7 breast cancer cells

Mol Med Rep. 2012 Jan;5(1):41-7. doi: 10.3892/mmr.2011.583. Epub 2011 Sep 9.

Abstract

The aim of this study was to explore the effect of bisphenol A (BPA) on the EGFR-STAT3 pathway in breast cancer. We applied 3-(4,5-dimethylthiazol-2-yl)2,5-diphenyl tetrazolium bromide (MTT) cytotoxicity assay to the analysis of the responsiveness of MCF-7 cells to BPA. Gene expression was assayed at the transcriptional and translational levels by reverse transcription-PCR and Western blotting. We explored the effects of BPA on MCF-7 cell proliferation through inhibition of the related genes, STAT3, using RNA interference, and EGFR, using its inhibitor AG1478. The optimal concentration and time point of BPA-induced proliferation in MCF-7 cells are 1 µM and 24 h, respectively. BPA significantly increased the expression of STAT3 at a concentration of 1 µM following treatment for 48 h and the expression of STAT3 was down-regulated after blocking EGFR. When STAT3 was blocked in MCF-7 cells, BPA did not appear to induce cell proliferation. Treatment with BPA (1 µM) in the presence of AG1478 for 48 h resulted in the stimulation of cell growth in MCF-7 cells, similar to that of the BPA alone treatment. BPA increases STAT3 expression, which is a major factor in the pathway of BPA-induced proliferation, and STAT3 activation contributes to BPA-induced breast cancer cell proliferation. However, EGFR mediates negative signaling for BPA-induced breast cancer cell proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds
  • Breast Neoplasms
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • ErbB Receptors / antagonists & inhibitors
  • ErbB Receptors / genetics
  • ErbB Receptors / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Phenols / pharmacology*
  • Quinazolines / pharmacology
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • STAT3 Transcription Factor / antagonists & inhibitors
  • STAT3 Transcription Factor / genetics
  • STAT3 Transcription Factor / metabolism*
  • Signal Transduction / drug effects
  • Time Factors
  • Tyrphostins / pharmacology

Substances

  • Benzhydryl Compounds
  • Phenols
  • Quinazolines
  • RNA, Small Interfering
  • STAT3 Transcription Factor
  • Tyrphostins
  • RTKI cpd
  • ErbB Receptors
  • bisphenol A