TY - JOUR
T1 - Transcriptome profiling reveals bisphenol A alternatives activate estrogen receptor alpha in human breast cancer cells
AU - Mesnage, Robin
AU - Phedonos, Alexia
AU - Arno, Matthew
AU - Balu, Sucharitha
AU - Corton, J. Christopher
AU - Antoniou, Michael
PY - 2017/8
Y1 - 2017/8
N2 - Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines. Estrogenicity was assessed (10−11M to 10−4M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer.
AB - Plasticizers with estrogenic activity, such as bisphenol A (BPA), have potential adverse health effects in humans. Due to mounting evidence of these health effects, BPA is being phased out and replaced by other bisphenol variants in “BPA-free” products. We have compared estrogenic activity of BPA to 6 bisphenol analogues (bisphenol S, BPS; bisphenol F, BPF; bisphenol AP, BPAP; bisphenol AF, BPAF; bisphenol Z, BPZ; bisphenol B, BPB) in three human breast cancer cell lines. Estrogenicity was assessed (10−11M to 10−4M) by cell growth in an estrogen receptor (ER)-mediated cell proliferation assay, and by the induction of estrogen response element-mediated transcription in a luciferase assay. BPAF was the most potent bisphenol, followed by BPB > BPZ ∼ BPA > BPF ∼ BPAP > BPS. The addition of ICI 182,780 antagonized the activation of ERs. Data mining of ToxCast high-throughput screening assays confirms our results but also shows divergence in the sensitivities of the assays. Gene expression profiles were determined in MCF-7 cells by microarray analysis. The comparison of transcriptome profile alterations resulting from BPA alternatives with an ERα gene expression biomarker further indicates that all BPA alternatives act as ERα agonists in MCF-7 cells. These results were confirmed by Illumina-based RNA sequencing. In conclusion, BPA alternatives are not necessarily less estrogenic than BPA in human breast cancer cells. BPAF, BPB, and BPZ were more estrogenic than BPA. These findings point to the importance of better understanding the risk of adverse effects from exposure to BPA alternatives, including hormone-dependent breast cancer.
U2 - 10.1093/toxsci/kfx101
DO - 10.1093/toxsci/kfx101
M3 - Article
SN - 1096-6080
VL - 158
SP - 431
EP - 443
JO - Toxicological sciences : an official journal of the Society of Toxicology
JF - Toxicological sciences : an official journal of the Society of Toxicology
ER -