Expression of line-1 retrotransposon induced by environmental pollutants in breast cancer cells

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

Bruselas

Congreso; 54th Congress of the European Societies of Toxicology, EUROTOX; 2018

Sociedades Europeas de Toxicología

Breast cancer is the most common cancer worldwide in women and different studies link pesticide exposure to the risk of developing this disease. The pesticides hexachlorobenzene (HCB) and chlorpyrifos (CPF) are weak ligands of the aryl hydrocarbon receptor (AhR), a transcription factor involved in apoptosis and proliferation. Transforming growth factor-β1 (TGF-β1) is activated during cancer development. We have postulated that alterations in AhR/TGF-β1 crosstalk might contribute to breast cancer progression. Epigenetic changes include retrotransposons like the long interspersed nuclear element 1 (LINE-1), which is activated in mammary tumors. Ligands of AhR can induce activation of LINE-1 and epithelial to mesenchymal transition, through the TGF-β1/Smad pathway. Our aim was to study the effect of HCB and CPF on LINE-1 expression and to elucidate whether the mechanism of action is related to the AhR/TGF-β1 interaction in human breast cancer cells MDA-MB-231. We have reported that HCB (0.005-5 μM) activates the AhR/c-Src signaling, and induces Smad pathway, promoting MDA-MB-231 migration and invasion. Our results showed that LINE-1 mRNA levels (RT-qPCR), were enhanced at 0.005 μM HCB (p