https://scholars.lib.ntu.edu.tw/handle/123456789/575366
標題: | Epigenetic influences of low-dose bisphenol A in primary human breast epithelial cells | 作者: | Weng Y.-I. Hsu P.-Y. Liyanarachchi S. Liu J. Deatherage D.E. Huang Y.-W. Zuo T. Rodriguez B. CHING-HUNG LIN ANN-LII CHENG Huang T.H.-M. |
公開日期: | 2010 | 卷: | 248 | 期: | 2 | 起(迄)頁: | 111-121 | 來源出版物: | Toxicology and Applied Pharmacology | 摘要: | Substantial evidence indicates that exposure to bisphenol A (BPA) during early development may increase breast cancer risk later in life. The changes may persist into puberty and adulthood, suggesting an epigenetic process being imposed in differentiated breast epithelial cells. The molecular mechanisms by which early memory of BPA exposure is imprinted in breast progenitor cells and then passed onto their epithelial progeny are not well understood. The aim of this study was to examine epigenetic changes in breast epithelial cells treated with low-dose BPA. We also investigated the effect of BPA on the ERα signaling pathway and global gene expression profiles. Compared to control cells, nuclear internalization of ERα was observed in epithelial cells preexposed to BPA. We identified 170 genes with similar expression changes in response to BPA. Functional analysis confirms that gene suppression was mediated in part through an ERα-dependent pathway. As a result of exposure to BPA or other estrogen-like chemicals, the expression of lysosomal-associated membrane protein 3 (LAMP3) became epigenetically silenced in breast epithelial cells. Furthermore, increased DNA methylation in the LAMP3 CpG island was this repressive mark preferentially occurred in ERα-positive breast tumors. These results suggest that the in vitro system developed in our laboratory is a valuable tool for exposure studies of BPA and other xenoestrogens in human cells. Individual and geographical differences may contribute to altered patterns of gene expression and DNA methylation in susceptible loci. Combination of our exposure model with epigenetic analysis and other biochemical assays can give insight into the heritable effect of low-dose BPA in human cells. ? 2010. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-77956900493&doi=10.1016%2fj.taap.2010.07.014&partnerID=40&md5=ee1b18fc35466dfe0f785dc36bbdfe9d https://scholars.lib.ntu.edu.tw/handle/123456789/575366 |
ISSN: | 0041-008X | DOI: | 10.1016/j.taap.2010.07.014 | SDG/關鍵字: | 4 nonylphenol; 4,4' isopropylidenediphenol; daidzein; diethylstilbestrol; estrogen receptor alpha; growth arrest and DNA damage inducible protein 45; lysosomal associated membrane protein 3; monocarboxylate transporter 1; protein; unclassified drug; 4,4' isopropylidenediphenol; benzhydryl derivative; estrogen; estrogen receptor alpha; LAMP3 protein, human; lysosome associated membrane protein; nuclear localization signal; phenol derivative; tumor protein; article; breast carcinogenesis; breast epithelium; cell nucleus; cell strain MCF 7; cellular distribution; controlled study; CpG island; DNA methylation; epigenetics; gene expression; gene expression profiling; human; human cell; human cell culture; in vitro study; protein localization; signal transduction; adolescent; adult; breast; drug effects; epithelium cell; female; genetic epigenesis; genetics; metabolism; nuclear localization signal; toxicity; tumor cell line; young adult; Adolescent; Adult; Breast; Cell Line, Tumor; Epigenesis, Genetic; Epithelial Cells; Estrogen Receptor alpha; Estrogens, Non-Steroidal; Female; Gene Expression; Humans; Lysosome-Associated Membrane Glycoproteins; Neoplasm Proteins; Nuclear Localization Signals; Phenols; Young Adult; Adolescent; Adult; Benzhydryl Compounds; Breast; Cell Line, Tumor; Epigenesis, Genetic; Epithelial Cells; Estrogen Receptor alpha; Estrogens, Non-Steroidal; Female; Gene Expression; Humans; Lysosome-Associated Membrane Glycoproteins; Neoplasm Proteins; Nuclear Localization Signals; Phenols; Young Adult |
顯示於: | 醫學系 |
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