The aryl hydrocarbon receptor agonists reactivate LINE-1 retrotransposon in breast cancer cells

LORENA ZÁRATE ; MARIANELA LASAGNA ; ANDREA RANDI ; ZAPPIA DANIEL; FLORENCIA CHIAPPINI ; FEDERICO MONCZOR; MIRET NOELIA; CAROLINA PONTILLO ; CLAUDIA COCCA

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

Sociedad Argentina de Investigación Clínica

Breast cancer is the most common cancer worldwide in women and Argentina is the second country of America with the highest mortality rate. Epigenetic changes are more frequent in breast cancer cells than genetic mutations. These alterations affect retrotransposons like the long interspersed nuclear element 1 (LINE-1), which is highly activated in breast tumors. Environmental pollutants ligands of aryl hydrocarbon receptor (AhR) can induce the activation of LINE-1 and epithelial to mesenchymal transition, through the transforming growth factor-β1 (TGF-β1)/Smad signaling pathway. AhR is a transcription factor that modulates processes such as apoptosis, proliferation and migration. We worked with environmental doses of two weak ligands of the AhR: the organochlorine pesticide hexachlorobenzene (HCB) and the organophosphate chlorpyrifos (CPF). Our aim was to study the effect of these pesticides on LINE-1 expression and to elucidate whether the mechanism of action is related to the interaction AhR/TGF-β1, in the human breast cancer cell line MDA-MB-231 (- estrogen receptor α). We have reported that HCB (0.005, 0.05, 0.5 y 5 μM) activates the AhR/c-Src signaling, which subsequently induces the TGF-β1/Smad pathway, promoting MDA-MB-231 cell migration and invasion. Our results showed that LINE-1 mRNA levels, evaluated by RT-qPCR, were enhanced at 0.005 μM HCB (p