Hexachlorobenzene induces cell proliferation and IGF-I signaling pathway in an estrogen receptor alpha-dependent manner in MCF-7 breast cancer cell line.
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.
García
María Alejandra
MA
Departamento de Bioquímica Humana, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Peña
Delfina
D
Alvarez
Laura
L
Cocca
Claudia
C
Pontillo
Carolina
C
Bergoc
Rosa
R
de Pisarev
Diana Kleiman
DK
Randi
Andrea
A
D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism; D053938:DNA Fragmentation / Q000187:drug effects; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation / Q000187:drug effects; D006581:Hexachlorobenzene / Q000633:toxicity*; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D010575:Pesticides / Q000633:toxicity*; D010766:Phosphorylation / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D011972:Receptor, Insulin / Q000378:metabolism; D018336:Receptors, Aryl Hydrocarbon / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D014443:Tyrosine / Q000378:metabolism
D047628:Estrogen Receptor alpha; C526292:IRS1 protein, human; D055504:Insulin Receptor Substrate Proteins; D010575:Pesticides; D012333:RNA, Messenger; D018336:Receptors, Aryl Hydrocarbon; D000077267:Fulvestrant; D014443:Tyrosine; D004958:Estradiol; D006581:Hexachlorobenzene; D007334:Insulin-Like Growth Factor I; D019363:Cytochrome P-450 CYP1A1; D011972:Receptor, Insulin