Skip Navigation

Publication Detail

Title: In Utero Exposure to Bisphenol a Promotes Mammary Tumor Risk in MMTV-Erbb2 Transgenic Mice Through the Induction of ER-erbB2 Crosstalk.

Authors: Ma, Zhikun; Parris, Amanda B; Howard, Erin W; Davis, Meghan; Cao, Xia; Woods, Courtney; Yang, Xiaohe

Published In Int J Mol Sci, (2020 Apr 28)

Abstract: Bisphenol A (BPA) is the most common environmental endocrine disrupting chemical. Studies suggest a link between perinatal BPA exposure and increased breast cancer risk, but the underlying mechanisms remain unclear. This study aims to investigate the effects of in utero BPA exposure on mammary tumorigenesis in MMTV-erbB2 transgenic mice. Pregnant mice were subcutaneously injected with BPA (0, 50, 500 ng/kg and 250 µg/kg BW) daily between gestational days 11-19. Female offspring were examined for mammary tumorigenesis, puberty onset, mammary morphogenesis, and signaling in ER and erbB2 pathways. In utero exposure to low dose BPA (500 ng/kg) induced mammary tumorigenesis, earlier puberty onset, increased terminal end buds, and prolonged estrus phase, which was accompanied by proliferative mammary morphogenesis. CD24/49f-based FACS analysis showed that in utero exposure to 500 ng/kg BPA induced expansion of luminal and basal/myoepithelial cell subpopulations at PND 35. Molecular analysis of mammary tissues at PND 70 showed that in utero exposure to low doses of BPA induced upregulation of ERα, p-ERα, cyclin D1, and c-myc, concurrent activation of erbB2, EGFR, erbB-3, Erk1/2, and Akt, and upregulation of growth factors/ligands. Our results demonstrate that in utero exposure to low dose BPA promotes mammary tumorigenesis in MMTV-erbB2 mice through induction of ER-erbB2 crosstalk and mammary epithelial reprogramming, which advance our understanding of the mechanism associated with in utero exposure to BPA-induced breast cancer risk. The studies also support using MMTV-erbB2 mouse model for relevant studies.

PubMed ID: 32353937 Exiting the NIEHS site

MeSH Terms: Animals; Benzhydryl Compounds/administration & dosage; Benzhydryl Compounds/adverse effects*; Cellular Reprogramming; Endocrine Disruptors/administration & dosage; Endocrine Disruptors/adverse effects*; Estrogen Receptor alpha/genetics; Estrogen Receptor alpha/metabolism; Female; Gene Expression Regulation, Neoplastic/drug effects; Gestational Age; Mammary Neoplasms, Experimental/chemically induced; Mammary Neoplasms, Experimental/genetics; Mammary Neoplasms, Experimental/pathology*; Mammary Tumor Virus, Mouse/pathogenicity; Maternal Exposure; Mice; Mice, Transgenic; Phenols/administration & dosage; Phenols/adverse effects*; Pregnancy; Prenatal Exposure Delayed Effects/chemically induced; Prenatal Exposure Delayed Effects/genetics; Prenatal Exposure Delayed Effects/pathology*; Receptor, ErbB-2/genetics; Receptor, ErbB-2/metabolism; Sexual Maturation/drug effects; Signal Transduction/drug effects*

Back
to Top