title: Effects of bisphenol A exposure on the proliferation and senescence of normal human mammary epithelial cells.
abstract: The carcinogenic activity of bisphenol A (BPA) is responsible for stimulating growth in estrogen-dependent breast cancer tissues, cell lines and rodent studies. However, it is not fully understood how this compound promotes mammary carcinogenesis. In our study, we examined the effect of BPA on cellular proliferation and senescence in human mammary epithelial cells (HMEC). Exposure to BPA for 1 week at the early stage at passage 8 increased the proliferation and sphere size of HMEC at the later stage up to passage 16, suggesting that BPA has the capability to modulate cell growth in breast epithelial cells. Interestingly, the number of human heterochromatin protein-1γ positive cells, which is a marker of senescence, was also increased among BPA-treated cells. Consistent with these findings, the protein levels of both p16 and cyclin E, which are known to induce cellular senescence and promote proliferation, respectively, were increased in BPA-exposed HMEC. Furthermore, DNA methylation levels of genes related to development of most or all tumor types, such as BRCA1, CCNA1, CDKN2A (p16), THBS1, TNFRSF10C and TNFRSF10D, were increased in BPA-exposed HMEC. Our findings in the HMEC model suggested that the genetic and epigenetic alterations by BPA might damage HMEC function and result in complex activities related to cell proliferation and senescence, playing a role in mammary carcinogenesis.
authors.affiliation: Health Risk Research Section, National Institute for Environmental Studies, Tsukuba, Japan.
authors.forename: Xian-Yang
authors.initials: XY
authors.lastname: Qin
authors.forename: Tomokazu
authors.initials: T
authors.lastname: Fukuda
authors.forename: Linqing
authors.initials: L
authors.lastname: Yang
authors.forename: Hiroko
authors.initials: H
authors.lastname: Zaha
authors.forename: Hiromi
authors.initials: H
authors.lastname: Akanuma
authors.forename: Qin
authors.initials: Q
authors.lastname: Zeng
authors.forename: Jun
authors.initials: J
authors.lastname: Yoshinaga
authors.forename: Hideko
authors.initials: H
authors.lastname: Sone
mesh_terms: D000395:Air Pollutants, Occupational / Q000633:toxicity*; D001559:Benzhydryl Compounds; D048708:Cell Growth Processes / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D042361:Mammary Glands, Human / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010636:Phenols / Q000633:toxicity*; D000098826:Bisphenol A Compounds
chemical_list: D000395:Air Pollutants, Occupational; D001559:Benzhydryl Compounds; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds