Hexachlorobenzene induces cell proliferation and IGF-I signaling pathway in an estrogen receptor α-dependent manner in MCF-7 breast cancer cell line

Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the biosphere. ER alpha regulates the expression of genes involved in growth and development, and plays an important role in breast cancer. The present study focuses attention on the effect of HCB (0.005, 0.05, 0.5, 5 mu M) on cell proliferation in estrogen receptor alpha (ER alpha)(+) MCF-7, and ER alpha(-) MDA-MB-231 breast cancer cell lines. We also studied the insulin growth factor-I (IGF-I) signaling pathway in MCF-7 cells. HCB (0.005 and 0.05 mu M) stimulated cell proliferation in MCF-7, but not in MDA-MB-231 cells. The pesticide increased apoptosis in MCF-7, at HCB (0.5 and 5 mu M). At these doses, HCB induced the expression of the aryl hydrocarbon receptor (AhR)-regulated gene cytochrome P4501A1. MCF-7 cells exposed to HCB (0.005 and 0.05 mu M) overexpressed IGF-IR and insulin receptor (IR). IRS-1-phosphotyrosine content was increased in a dose dependent manner. ICI 182,780 prevented HCB-induced cell proliferation and IGF-I signaling in MCF-7 cells incubated in phenol-red free media. In addition, HCB (0.005 mu M) increased c-Src activation, Tyr537-ER alpha phosphorylation and ER alpha down-regulation. Taken together, Our data indicate that HCB stimulation of cell proliferation and IGF-I signaling is ER alpha dependent in MCF-7 cells. (C) 2009 Elsevier Ireland Ltd. All rights reserved.