Expression profiling of estrogen responsive genes on bisphenol A, 4-nonylphenol and 17 beta-estradiol treatment using in house cDNA microarray

Abstract

Bisphenol A (BPA) and nonylphenol (NP) are thought to mimic estrogens in their action, and are called endocrine disrupting chemicals. These phenolic chemicals are used in a number of commercial products and have been reported to be weakly estrogenic in previous studies. Their estrogenic activities are mainly dependent on their binding affinity for the estrogen receptors in vitro and in vivo. To identify genes elicited by BPA and NP, we carried out a microarray analysis in MCF-7 cells treated with BPA and NP using human c-DNA microarray including 416 endocrine system related genes. At the minimum fold-change criteria of 1.5, 14 and 29 genes were identified showing significant changes in gene expression resulting from BPA and NP, respectively. Especially, 2 genes were repressed and 6 genes were induced by BPA and NP as 17 beta-estradiol (E2). To validate the gene expression profiles identified from microarray analyses, the expression patterns of 4 representative genes, Selenoprotein P, plasma, 1 (SEPP1), Matrix G1a protein (MOP), H2A histone family, member X (H2AFX) and breast cancer 1, early onset (BRCA1) were examined by real time RT-PCR. We further examined the expression patterns of phthalic chemicals with estrogenic activity by comparing with those of E2 or phenolic chemicals to evaluate that alterations of these estrogen responsive genes may act as useful biomarkers to the endocrine disrupting chemicals with estrogenic activity.