Bisphenol A Induces Migration through a GPER-, FAK-, Src-, and ERK2-Dependent Pathway in MDA-MB-231 Breast Cancer Cells

Chem Res Toxicol. 2016 Mar 21;29(3):285-95. doi: 10.1021/acs.chemrestox.5b00457. Epub 2016 Mar 7.


Bisphenol A (BPA) is an industrial synthetic chemical utilized in the production of numerous products including food and beverage containers. Humans are exposed to BPA during ingestion of contaminated water and food because it can leach from polycarbonate containers, beverage cans, and epoxy resins. BPA has been related with the development of several diseases including breast cancer. However, the signal transduction pathways mediated by BPA and its role as a promoter of migration and invasion in breast cancer cells remain to be investigated. Here, we demonstrate that BPA promotes migration, invasion, and an increase in the number of focal contacts in MDA-MB-231 breast cancer cells. Moreover, MDA-MB-231 cells express GPER, and BPA promotes migration through a GPER-dependent pathway. BPA also induces activation of FAK, Src, and ERK2, whereas migration induced by BPA requires the activity of these kinases. In addition, BPA induces an increase on AP-1- and NFκB-DNA binding activity through an Src- and ERK2-dependent pathway. In conclusion, our findings demonstrate, that BPA induces the activation of signal transduction pathways, which mediate migration, AP-1/NFκB-DNA binding activity, and an invasion process in MDA-MB-231 breast cancer cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Benzhydryl Compounds / pharmacology*
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Movement / drug effects*
  • Cell Survival / drug effects
  • Female
  • Focal Adhesion Kinase 1 / metabolism*
  • Humans
  • Mitogen-Activated Protein Kinase 1 / metabolism*
  • Molecular Structure
  • Phenols / pharmacology*
  • Receptors, G-Protein-Coupled / metabolism*
  • Structure-Activity Relationship
  • Tumor Cells, Cultured
  • src-Family Kinases / metabolism*


  • Benzhydryl Compounds
  • Phenols
  • Receptors, G-Protein-Coupled
  • Focal Adhesion Kinase 1
  • PTK2 protein, human
  • src-Family Kinases
  • MAPK1 protein, human
  • Mitogen-Activated Protein Kinase 1
  • bisphenol A