Modulation of the expression of bloom helicase by estrogenic agents

Abstract

We report that the expression of Bloom helicase (BLM) was up-regulated by 17β-estradiol (E2) in estrogen receptor (ER)-positive mammary tumor MCF-7 cells, but was hardly modulated in ER-negative mammary tumor MDA-MB-231 cells. ER antagonist ICI182780 blocked the E2 effect on BLM expression in MCF-7 cells. From these results we conclude that ER participates in up-regulation of BLM expression in MCF-7 cells by means of E2. Similar results were obtained when MCF-7 cells were treated with bisphenol A (BPA), an endocrine-disrupting chemical having a weak estrogenic activity. The ER binding ability of BPA is estimated at 1/1000 of E2 ability, and in this study about 1000-times more BPA was needed for the same levels of estrogenic effect of E2. The expression of cell-cycle associated genes, cdc6, MCM5, MCM2, Myt1, PCNA and AuroraA were up-regulated by E2 and BPA treatment in MCF-7 cells accompanied by up-regulation of BLM. In this BLM promoter study, Sp1 elements in the upper region of BLM modulated transcription, but were not indispensable for E2 response. Our results suggested that up-regulation of BLM expression by E2 and BPA is ER-dependent and may be responsible for repair of DNA damage caused by the genotoxicity of these estrogenic agents. © 2007 Pharmaceutical Society of Japan.