ACSL4 PROMOTER CHARACTERIZATION AND REGULATION BY SHP2 IN BREAST CANCER CELLS

LÓPEZ P.; DATTILO M.; BENZO Y.; ORLANDO U; PODEROSO C; CORNEJO MACIEL F; PODESTÁ EJ; MALOBERTI PM

Cordoba

Congreso; LII REUNIÓN SAIB 2016; 2016

SAIB

In breast cancer Acyl-CoA synthetase 4 (ACSL4) and the tyrosine phosphatase SHP2 play a role on tumor aggressiveness. ACSL4 is up-regulated in triple negative breast cancer cell lines and tumors. In order to study the mechanism involved in the regulation of expression of the enzyme, we previously showed differences in ACSL4 promoter regulation in MDA-MB-231 and MCF-7, being 3´end a possible responsible region of its over expression in MDA-MB-231. In this work we demonstrated by successive deletions of the promoter leaving fixed one end, that the last 43 bp of the 3´ end is a positive regulatory region only in MDA-MB-231. By Genomatix tool, we identified transcription factors consensus sites on the promoter. Results of RORα mutant site suggest it is involved in the inhibition in the 5´ end in both cell lines. Results of E2F transcription factor 2 mutant sites showed it could enhance the promoter activity in the 3´ end only in MDA-MB-231. Moreover, we treated MCF-7 with estradiol benzoate and a decrease in promoter activity was observed, effect reversed by ICI 182780. We expressed ERα in MDA-MB-231 and had a signal decrease, suggesting this receptor is responsible of the estrogenic effect. We demonstrated that the MEK signaling pathway could be involved in the regulation of ACSL4. We also demonstrated a role of SHP2 on ACSL4 expression and promoter activity in breast cancer cells.