Epigenetic changes induced by exposure to ligands of aryl hydrocarbon receptor and breast cancer

ZAPPIA D; ZARATE LV; MONCZOR F; MIRET NV; GOMEZ AL; LASAGNA M; KASS L; ALTAMIRANO GA; PONTILLO CA; COCCA C; RANDI AS

Mar del Plata

Congreso; LXIV Reunión Científica Anual de la Sociedad Argentina de Investigación Clínica; 2019

Sociedad Argentina de Investigación Clínica

Breast cancer is the main cause of cancer death among women and epigenetic changes contribute to the disease. These alterations include the demethylation and activation of the long interspersed nuclear element 1 (LINE-1) retrotransposon, which has been linked to tumor progression. Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1, through transforming growth factor-β1 (TGF-β1)/Smad pathway. This study analyzed the effect of two weak ligands of the AhR on LINE-1 expression and the role of AhR and TGF-β1 in their mechanism of action. The human breast cancer cell line MDA-MB-231 was exposed to the organochlorine pesticide hexachlorobenzene (HCB) or the organophosphate chlorpyrifos (CPF). Both activated the AhR/c-Src/Smad axis and enhanced LINE-1 mRNA levels (0.05-50 μM CPF, 0.005 μM HCB, p