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National Institute of Environmental Health Sciences

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Your Environment. Your Health.

Publication Detail

Title: Bisphenol AF promotes estrogen receptor-positive breast cancer cell proliferation through amphiregulin-mediated crosstalk with receptor tyrosine kinase signaling.

Authors: Zhao, Qingxia; Howard, Erin W; Parris, Amanda B; Ma, Zhikun; Xing, Ying; Yang, Xiaohe

Published In PLoS One, (2019)

Abstract: Exposure to bisphenol A (BPA), an endocrine-disrupting compound, is associated with increased risk of estrogen-related diseases, including estrogen receptor-positive (ER+) breast cancer. Although bisphenol analogs, i.e. bisphenol AF (BPAF), have replaced BPA in industrial settings, increasing data indicate that these alternatives may have similar or even more potent estrogenic effects. As such, BPAF exhibits increased ER binding affinities than BPA in biochemical assays. However, preclinical studies exploring the effects of BPAF on ER+ breast cancer are missing mechanistic data. Thus, we aimed to characterize the effects of BPAF on MCF-7 and T47D ER+ breast cancer cells with mechanistic insight. We found that BPAF promoted cell growth and cell cycle progression concurrently with BPAF-induced ERα transcriptional activity and ER-RTK signaling activation. ER signaling blockage revealed that BPAF-induced cell proliferation and ER-RTK crosstalk were ER-dependent. Gene expression data demonstrated that AREG is a sensitive target of BPAF in our in vitro models. Importantly, we determined that AREG upregulation is necessary for BPAF-induced cellular responses. Ultimately, our novel finding that AREG mediates BPAF-induced ER-RTK crosstalk in ER+ breast cancer cells supports future studies to characterize the impact of BPAF on human ER+ breast cancer risk and to assess the safety profile of BPAF.

PubMed ID: 31059536 Exiting the NIEHS site

MeSH Terms: Amphiregulin/metabolism*; Benzhydryl Compounds/pharmacology*; Breast Neoplasms/metabolism*; Breast Neoplasms/pathology; Cell Proliferation/drug effects*; Estrogen Receptor alpha/metabolism*; Female; Humans; MCF-7 Cells; Phenols/pharmacology*; Proto-Oncogene Proteins B-raf/metabolism*; Signal Transduction/drug effects*

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