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

C VENTURA; N MIRET; A RANDI; C COCCA; MR RAMOS NIETO; M NUÑEZ

Mar del Plata

Congreso; LXI Reunión anual de la Sociedad Argentina de Investigación Clínica; 2016

Sociedad Argentina de Investigación Clínica (SAIC)

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 h of exposure. c-SRC and ERα participation was evaluated using specific inhibitors (1µM PP2 or 1 nM ICI 182,780, respectively). Results: We observed a slight increment of 418-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 Insulin-like growth factor 1-receptor (IGF-1Rβ) phosphorylation promoted by 0.05 µM CPF until 30 minutes of exposure (p