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

Bisphenol A stimulates the epithelial mesenchymal transition of estrogen negative breast cancer... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Biochemistry and Biophysics Elsevier

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

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Publisher
Elsevier
Copyright
Copyright © 2015 Elsevier Inc.
ISSN
0003-9861
eISSN
1096-0384
D.O.I.
10.1016/j.abb.2015.09.006
Publisher site
See Article on Publisher Site

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.

Journal

Archives of Biochemistry and BiophysicsElsevier

Published: Nov 1, 2015

References

  • Epidemiology of health disparities in relation to the biology of estrogen receptor-negative breast cancer
    Agurs-Collins, T.; Dunn, B.K.; Browne, D.; Johnson, K.A.; Lubet, R.
  • Mesothelin enhances invasion of ovarian cancer by inducing MMP-7 through MAPK/ERK and JNK pathways
    Chang, M.C.; Chen, C.A.; Chen, P.J.; Chiang, Y.C.; Chen, Y.L.; Mao, T.L.; Lin, H.W.; Lin Chiang, W.H.; Cheng, W.F.
  • Breast cancer statistics, 2013
    Desantis, C.; Ma, J.; Bryan, L.; Jemal, A.
  • Signaling related with biphasic effects of bisphenol A (BPA) on Sertoli cell proliferation: a comparative proteomic analysis
    Ge, L.C.; Chen, Z.J.; Liu, H.; Zhang, K.S.; Su, Q.; Ma, X.Y.; Huang, H.B.; Zhao, Z.D.; Wang, Y.Y.; Giesy, J.P.; Du, J.; Wang, H.S.
  • Bisphenol A (BPA) in China: a review of sources, environmental levels, and potential human health impacts
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  • FOXA1 is an independent prognostic marker for ER-positive breast cancer
    Mehta, R.J.; Jain, R.K.; Leung, S.; Choo, J.; Nielsen, T.; Huntsman, D.; Nakshatri, H.; Badve, S.
  • Forkhead box A1 (FOXA1) is a key mediator of insulin-like growth factor I (IGF-I) activity
    Potter, A.S.; Casa, A.J.; Lee, A.V.
  • Human exposure to bisphenol A (BPA)
    Vandenberg, L.N.; Hauser, R.; Marcus, M.; Olea, N.; Welshons, W.V.
  • EMT, the cytoskeleton, and cancer cell invasion
    Yilmaz, M.; Christofori, G.

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