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

Abstract:

:Hexachlorobenzene (HCB) is an organochlorine pesticide widely distributed in the biosphere. ERalpha 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 microM) on cell proliferation in estrogen receptor alpha (ERalpha)(+) MCF-7, and ERalpha(-) 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 microM) 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 microM). 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 microM) 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 microM) increased c-Src activation, Tyr537-ERalpha phosphorylation and ERalpha down-regulation. Taken together, our data indicate that HCB stimulation of cell proliferation and IGF-I signaling is ERalpha dependent in MCF-7 cells.

journal_name

Toxicol Lett

journal_title

Toxicology letters

authors

García MA,Peña D,Alvarez L,Cocca C,Pontillo C,Bergoc R,de Pisarev DK,Randi A

doi

10.1016/j.toxlet.2009.10.026

subject

Has Abstract

pub_date

2010-02-01 00:00:00

pages

195-205

issue

2

eissn

0378-4274

issn

1879-3169

pii

S0378-4274(09)01481-7

journal_volume

192

pub_type

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