Format

Send to

Choose Destination
Arch Biochem Biophys. 2015 Nov 1;585:10-16. doi: 10.1016/j.abb.2015.09.006. Epub 2015 Sep 9.

Bisphenol A stimulates the epithelial mesenchymal transition of estrogen negative breast cancer cells via FOXA1 signals.

Author information

1
Medical School, Foshan University, Foshan 528000, China. Electronic address: zhangxlfsu@126.com.
2
Department of Microbial and Biochemical Pharmacy, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
3
Medical School, Foshan University, Foshan 528000, China.

Abstract

Estrogen receptor negative (ER-) breast cancer are associated with increased risks for metastasis and high rates of recurrence. Our present study revealed that nanomolar bisphenol A (BPA), a typical endocrine disrupting chemical, promoted the in vitro migration and induced mesenchymal transition (EMT) of ER-breast cancer cells. PCR array revealed that BPA can down regulate 12 and up regulate 2 genes involved in regulation of signal transduction and biological pathways of breast cancer. The down regulated genes included FOXA1, which is a key determinant of endocrine response and down regulated by BPA via a time dependent manner. Silencing of FOXA1 by siRNA triggered the EMT of SkBr3 cells. While over expression of FOXA1 abolished BPA induced EMT. Further, 10(-8) M BPA significantly increased the phosphorylation of ERK1/2, p38-MAPK, and Akt in SkBr3 cells, while only PI3K/Akt inhibitor LY294002 attenuated the BPA induced down regulation of FOXA1 and E-Cadherin (E-Cad). Over expression of Akt also suppressed FOXA1 expression in SkBr3 cells. It suggested that PI3K/Akt mediated, at least partially, BPA induced EMT of ER-breast cancer cells. In summary, our data provided the first evidence that BPA can promote the EMT of ER-breast cancer cells through down regulation of FOXA1.

KEYWORDS:

BPA; Breast cancer cells; EMT; FOXA1

PMID:
26363213
DOI:
10.1016/j.abb.2015.09.006
[Indexed for MEDLINE]

Publication type, MeSH terms, Substances

Publication type

MeSH terms

Substances

Supplemental Content

Full text links

Icon for Elsevier Science
Loading ...
Support Center