INVESTIGADORES
COCCA Claudia Marcela
congresos y reuniones científicas
Título:
Organochlorine pesticides induce changes in insulin growth factors signaling pathway in breast cancer cell lines
Autor/es:
MARÍA ALEJANDRA GARCÍA; CLAUDIA COCCA; DELFINA PEÑA; ROSA BERGOC; DIANA KLEIMAN; ANDREA RANDI
Lugar:
Montreal, Canada
Reunión:
Congreso; 25 Congress of the International Association for Breast Cancer Research; 2006
Resumen:
Hexachlorobenzene (HCB)
is a widespread environmental pollutant. Chronic administration of HCB to
experimental animals elicits hypothyroxinemia, and liver and thyroid
carcinogenesis. We have previously demonstrated that HCB administration to rats
decreased uterine estrogen receptor levels and reduced circulating estradiol,
and enhanced the development and malignancy of
NMU-induced mammary tumors in rats and altered
insulin/IGF-I signaling pathway. The aim of this work is to compare the effects
of HCB on: 1-cellular proliferation, 2- Isulin Receptor (IR) and Insulin Growth
FactorI Receptor (IGF-IR) protein contents and 3-Insulin Receptor Substrate-1
(IRS-1) protein levels and its phosphorylation in Estrogen Receptor (ER)-positive MCF-7 and
ER-negative MDA-MB231 cell lines. The cells were grown in RPMI 1%
antibiotic-antimicotic, glutamine and 10% FBS, and were exposed to HCB (0,
0.005, 0.05, 0.5 and 5 microM). For proliferation assays, cells were exposed
for 7 days, and the number of colonies were counted. To evaluate receptor levels, cells were treated with HCB for 24
hours and cellular lysates were analysed by immunoblot. The results showed that
in MCF-7, HCB: a) enhanced cellular proliferation at 0.05microM, (p<0.001), b) decreased IGF-IR at 0.5 microM, (p<0.01), increased IR levels at 0.005 and 0.05mM, (p<0.05) and decreased IRS-1 content at 0.005, 0.5 and 5microM, (p<0.05). Its phosphorylation was augmented at 0.05microM, (p<0.05). In MDA-MB-231cells, HCB: a) had no effect on
proliferation, b) decreased IGF-IR at 0.005, 0.5 and 5mM, (p<0.05), increased IR levels at 0.05microM, (p<0.05) and increased IRS-1 content at 0.5 and 5microM. Thse results indicate different effects of HCB on the insulin/IGF-I
signaling pathway in ER-positive and ER-negative breast cancer cell lines.