Study On ER-mediated Estrogenic Effect Of Dechlorane Plus

Dechlorane plus(DP)is a high production volume chlorinated flame retardant.It has been detected in various environmental matrices and can be bioaccumulated in different bio tissues,especially in gonads.Our previous study has demonstrated the estrogenic effect of DP.DP could promote human breast cancer cell MCF-7 proliferation and induce the expression of estrogen receptor(ER)and MAPK/ERK pathway target genes.However,the underlying mechanism of DP is largely unknown,which will be investigated in the present study.ER-negative human breast cancer cell MDA-MB-231 and ER-positive human breast cancer cell MCF-7 were used for in vitro exposure.Whether the estrogenic effect of DP is mediated by ER will firstly be determined.Based on the results obtained,ER-mediated genomic and non-genomic pathways will be verified.Our results demonstrated DP could not induce the proliferation of ER-negative human breast cancer cell MDA-MB-231,suggesting the estrogenic effect of DP was primarily mediated by ER.Quantitative analysis of ER isoforms on-cytomembrane or within-nucleus,as well as transcriptional activation assay was carried out in the genomic pathway study.Results suggested DP could up-regulate the expression of estrogen receptor α(ERα),and binding to the dimerized-ERα,which could interact with estrogen responsive element(ERE)and cause estrogenic effects.However,DP could not activate the phosphorylation of ERa in the nucleus.Further investigation on non-genomic pathway proved the estrogenic effect of DP may be induced via the direct activation of MAPK/ERK pathway.Our results provided in this study will provide theoretical basis for toxicological and biological risk assessment of DP.