Identification of estrogenic genes responding to phthalate esters treatment in human MCF-7 cells

Abstract

The phthalate esters represent a class of chemicals used widely and diversely in industries as a plasticizer for elasticity and adhesion. Some phthalate diesters are classified as endocrine disrupting chemicals (EDCs), because they have been found weakly estrogenic. This study aimed to identify the changes of gene expression profiles by BBP, DBP, and DEHP using cDNA microarray. Firstly, we have selected the MCF-7 cell line, mainly used to estrogenic related research and selected the doses appearing the highest estrogenicity in E-screen assay to examine the estrogenicity and gene expression profiles of phthalate esters. Total RNA was isolated from cells treated with each phthalate esters (BBP, DBP, and DEHP) and 17 beta-estradiol, and then changes of gene expression were analyzed using cDNA microarray (KISTCHIP-400). This microarray includes 416 endocrine related genes based on public database and research papers. For the microarray analysis, genes that showed a 1.5-fold or greater change in their expression level (increase or decrease) were detected as differentially expressed genes (DEGs). Of the 416 genes analyzed, 95, 26, and 63 genes were identified showing significant changes in gene expression resulting from BBP, DBP, and DEHP. respectively. Among these genes, 11 genes, including MGP, SEPP1, and BAK1 were induced by more than 2 of 3 phthalate esters compared with 17 beta-estradiol. Therefore, it suggests that these genes may be associated with estrogenic effect of the phthalate esters on transcriptional level.