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Article Publish Status: FREE
Abstract Title:

Repeated exposure to 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), an active metabolite of bisphenol A, aggressively stimulates breast cancer cell growth in an estrogen receptorβ (ERβ)-dependent manner.

Abstract Source:

Mol Pharmacol. 2018 Dec 14. Epub 2018 Dec 14. PMID: 30552153

Abstract Author(s):

Masayo Hirao-Suzuki, Shuso Takeda, Katsuhiro Okuda, Masufumi Takiguchi, Shin'ichi Yoshihara

Article Affiliation:

Masayo Hirao-Suzuki

Abstract:

Bisphenol A (BPA), recognized as an endocrine disruptor, is thought to exert its activity through a mechanism involving the activation of estrogen receptors (ERα/β). However, a major problem is that very high concentrations of BPA are required (i.e., those in excess of environmental levels) for effective activation of ERα/β-mediated transcriptional activities in vitro, despite the BPA-induced estrogenic effects observed in vivo. To elucidate the causalreasons, we successfully identified a BPA metabolite, 4-methyl-2,4-bis(4-hydroxyphenyl)pent-1-ene (MBP), which exhibits highly potent estrogenic activity both in vivo and in vitro. We have focused on the biological relationship between breast tumor promotion and MBP/BPA, because BPA is considered to be a human carcinogen owing to its breast tumor-promoting properties. In general, humans are exposed to many endocrine disruptors, including BPA. In the present study, we used the ERα/β-positive human breast cancer cell line, MCF-7, as an experimental model to investigate the effects of repeatedexposure to BPA/MBP at concentrations found in the environment on the expression of ERα/β and to determine the particular ER subtype involved. We demonstrated that repeated exposure to MBP, but not to BPA, significantly downregulated ERα protein expression and stimulated the proliferation of MCF-7 cells through the activation of ERβ-mediated signaling.

Study Type : In Vitro Study

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