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

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.

• Authors: Xiao-Lin Zhang, Hong-Sheng Wang, Na Liu, Li-Chen Ge
• Journal: Archives of biochemistry and biophysics (Arch Biochem Biophys) Vol. 585 Pg. 10-16 (Nov 01 2015) ISSN: 1096-0384 [Electronic] United States
• PMID: 26363213 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• Benzhydryl Compounds
• Cadherins
• Chromones
• ESR1 protein, human
• Endocrine Disruptors
• Enzyme Inhibitors
• Estrogen Receptor alpha
• FOXA1 protein, human
• Hepatocyte Nuclear Factor 3-alpha
• Morpholines
• Phenols
• RNA, Small Interfering
• 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
• Proto-Oncogene Proteins c-akt
• MAPK1 protein, human
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• bisphenol A

Topics

• Benzhydryl Compounds (pharmacology)
• Cadherins (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement (drug effects)
• Chromones (pharmacology)
• Endocrine Disruptors (pharmacology)
• Enzyme Inhibitors (pharmacology)
• Epithelial Cells (drug effects, metabolism, pathology)
• Epithelial-Mesenchymal Transition (drug effects)
• Estrogen Receptor alpha (deficiency, genetics)
• Female
• Gene Expression Regulation, Neoplastic
• Hepatocyte Nuclear Factor 3-alpha (antagonists & inhibitors, genetics, metabolism)
• Humans
• Mammary Glands, Human (drug effects, metabolism, pathology)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Morpholines (pharmacology)
• Phenols (pharmacology)
• Phosphatidylinositol 3-Kinases (genetics, metabolism)
• Phosphorylation (drug effects)
• Proto-Oncogene Proteins c-akt (genetics, metabolism)
• RNA, Small Interfering (genetics, metabolism)
• Signal Transduction
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)