Hypomethylation of LINE-1 retrotransposon in breast cancer cells exposed to pesticides. Role of TGF-β1 pathway

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

Mar del Plata

Congreso; Reunión Anual de Sociedades de Biociencias; 2019

Sociedad Argentina de Investigación Clínica

Long interspersed nuclear element 1 (LINE-1)is the most common non-LTR retrotransposon in the human genome and comprises 17% of the genome. Reactivation of LINE-1 has been linked to breast cancer progression and metastasis.Strong ligands of aryl hydrocarbon receptor (AhR) activate LINE-1 through the transforming growth factor-β1 (TGF-β1)pathway in human liver cancer cells. We have observed that environmental doses of two weak AhR ligands: the organochlorine pesticide hexachlorobenzene (HCB, 0.005 μM) and the organophosphate chlorpyrifos (CPF, 0.5 μM) activate the TGF-β1 signaling and enhance LINE-1 mRNA expression in the human breast cancer cell line MDA-MB-231 .Our aim was to investigatethe role of the TGF-β1 signaling in the mechanism of action and if the pesticides induce epigenetic changes. To study the involvement of the TGF-β1 signaling on LINE-1 expression, cells were exposed to HCB or CPF in the presence of the TGF-β1 receptor I inhibitor (SB431542, 2 µM). qPCR results showed that the enhancement exerted by the pesticides was prevented by the treatment with the inhibitor (p