人前列腺细胞中低剂量双酚A（BPA）暴露的全基因组分析
Genome-Wide Analysis of Low Dose Bisphenol-A (BPA) Exposure in Human Prostate Cells.
作者信息
Renaud Ludivine, Huff Matthew, da Silveira Willian A, Angert Mila, Haas Martin, Hardiman Gary
机构信息
1Department of Medicine, Medical University of South Carolina, Charleston, SC, USA; 2MUSC Bioinformatics, Center for Genomic Medicine, Medical University of South Carolina, Charleston, SC, USA; 3MS in Biomedical Sciences Program, Medical University of South Carolina, Charleston, SC, USA; 4School of Biological Sciences and Institute for Global Food Security, Queens University Belfast, BelfastBT9 5AG, UK; 5Department of Medicine, University of California, La Jolla, CA, USA; 6Moores UCSD Cancer Center, University of California San Diego, La Jolla, California, CA, USA; 7Division of Biological Sciences, University of California San Diego, La Jolla, California, CA, USA.
出版信息
Curr Genomics. 2019 May;20(4):260-274. doi: 10.2174/1389202920666190603123040.
UNLABELLED
Endocrine disrupting compounds (EDCs) have the potential to cause adverse effects on wild-life and human health. Two important EDCs are the synthetic estrogen 17α-ethynylestradiol (EE2) and bisphenol-A (BPA) both of which are xenoestrogens (XEs) as they bind the estrogen receptor and dis-rupt estrogen physiology in mammals and other vertebrates. In the recent years the influence of XEs on oncogenes, specifically in relation to breast and prostate cancer has been the subject of considerable study.
METHODOLOGY
In this study, healthy primary human prostate epithelial cells (PrECs) were exposed to environmentally relevant concentrations of BPA (5nM and 25nM BPA) and interrogated using a whole genome microarray.
RESULTS
Exposure to 5 and 25nM BPA resulted in 7,182 and 7,650 differentially expressed (DE) genes, respectively in treated PrECs. Exposure to EE2 had the greatest effect on the PrEC transcriptome (8,891 DE genes).
CONCLUSION
We dissected and investigated the nature of the non-estrogenic gene signature associated with BPA with a focus on transcripts relevant to epigenetic modifications. The expression of transcripts encoding nuclear hormone receptors as well as histone and DNA methylation, modifying enzymes were significantly perturbed by exposure to BPA.
未标记
内分泌干扰化合物（EDCs）有可能对野生动物和人类健康造成不利影响。两种重要的EDCs是合成雌激素17α-乙炔雌二醇（EE2）和双酚A（BPA），它们都是外源性雌激素（XEs），因为它们能与雌激素受体结合，并扰乱哺乳动物和其他脊椎动物的雌激素生理功能。近年来，XEs对癌基因的影响，特别是与乳腺癌和前列腺癌相关的影响，一直是大量研究的主题。
方法
在本研究中，将健康的原代人前列腺上皮细胞（PrECs）暴露于环境相关浓度的BPA（5nM和25nM BPA），并使用全基因组微阵列进行检测。
结果
暴露于5nM和25nM BPA分别导致处理后的PrECs中有7182个和7650个差异表达（DE）基因。暴露于EE2对PrEC转录组的影响最大（8891个DE基因）。
结论
我们剖析并研究了与BPA相关的非雌激素基因特征的性质，重点关注与表观遗传修饰相关的转录本。暴露于BPA会显著扰乱编码核激素受体以及组蛋白和DNA甲基化修饰酶的转录本的表达。
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