Efeitos transformantes do bisfenol-A e medroxiprogesterona em células epiteliais da mama

Abstract

Bisphenol-A (BPA) and medroxyprogesterone acetate (MPA) are disruptor s hormone and hormone responsible for changes in proliferation, apoptosis, cell migration and invasion that contribute to the development and progression of breast cancer. Breast epithelial cells, MCF- 10A, were treated with BPA 1 μM or 10 μM for 12 days. On the 12th day it was associated with MPA for 96 hours and cell cultures analyzed by flow cytometry to verify the presence of base to breast cancer proteins. To assess invasiveness of cells treated with BPA and MPA was performed in Transwell invasion assay with Matrigel® and SDF-1α/CXCL12. Polymerase Chain Reaction (PCR) was performed and expression of some genes related to epithelial mesenchymal transition proven. BPA 10 μM/MPA induced the expression of CXCR4 and other factors related to invasion as metalloproteinases 2 and 9 (MMPs). The treated cells showed increased invasiveness in the presence of SDF-1α ligand for CXCR4. However, there are small changes in growth factor receptors such as EGFR1 decreased and increased HER2. Increased migration and invasion raise suspicion loss of epithelial characteristics of MCF-10A. Therefore, we investigated whether the expression of the epithelial marker E-cadherin and it was observed that treatment with BPA 10 μM/MPA had the greatest reduction in the expression of adhesion molecule. BPA/MPA had the ability to alter MCF-10A in vitro, conferring tumor properties, such as increased expression of proteins involved in metastasis, increased migration capacity, down-regulation of CDH1 (epithelial marker gene), increased expression CDH2 the gene considered mesenchymal marker and degradation of extracellular matrix by the expression of MMP-2 and MMP-9.