The pesticide Chlorpyrifos induces estrogen receptor alpha-dependent and -independent cell signaling pathways in the breast cancer cell line MCF-7

VENTURA CLARA; MARIA ROSA RAMOS NIETO; NOELIA MIRET; ANDREA RANDI; NÚÑEZ MARIEL; CLAUDIA COCCA

Congreso; LXI Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica

Chlorpyrifos (CPF) is one of the most widely used pesticides worldwide. We demonstrated that relevant environmental concentrations of CPF induce MCF-7 breast cancer cell proliferation via estrogen receptor alpha (ERα) phosphorylation. However, there are not evidences indicating if CPF activates another cell signaling pathways that lead to ERα phosphorylation. Objective: Our aim was to study the effect of CPF on cell signaling related to ERα and the role on CPF induced cell proliferation in MCF-7 cells. Methods: Cells were exposed to CPF (0.05 or 50 μM) for different periods. Protein phosphorylation was assayed by Western Blot using specific antibodies or by immunoprecipitation and blotting using anti-phosphotyrosine antibody. Cell proliferation was measured using mitotic index after 10 hours of exposure. C-Src and ERα participation was evaluated using specific inhibitors (1 μM PP2 or 1nM ICI 182,780, respectively). Results: We observed a slight increment of 416- tyrosine phosphorylation of c-Src induced by 0.05 μM CPF after 1 h of exposure, however, cell proliferation induced by this concentration of the pesticide could not be reverted by PP2. We have also detected an increment of β-subunit of Insulin-like growth factor 1 receptor (IGF1-Rβ) phosphorylation promoted by 0.05 μM CPF until 30 minutes of exposure (p