ACSL4 PROMOTER CHARACTERIZATION AND REGULATION BY SHP2 IN BREAST CANCER CELLS

LOPEZ PAULA; DATTILO MELINA; BENZO YANINA; ORLANDO ULISES; PODEROSO CECILIA; CORNEJO M. FABIANA; PODESTA ERNESTO; MALOBERTI PAULA

Congreso; 52th Annual Meeting Argentine Society for Biochemistry and Molecular Biology; 2016

In breast cancer Acyl-CoA synthetase 4 (ACSL4) and thetyrosine phosphatase SHP2 play a role on tumor aggressiveness. ACSL4 isup-regulated in triple negative breast cancer cell lines and tumors. In orderto study the mechanism involved in the regulation of expression of the enzyme,we previously showed differences in ACSL4 promoter regulation in MDA-MB-231 andMCF-7, being 3?L end a possible responsible region of its over expression inMDA-MB-231. In this work we demonstrated by successive deletions of thepromoter leaving fixed one end, that the last 43 bp of the 3?L end is a positiveregulatory region only in MDA-MB-231. By Genomatix tool, we identifiedtranscription factors consensus sites on the promoter. Results of ROR?¿ mutantsite 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 thepromoter activity in the 3´ end only in MDA-MB-231. Moreover, we treated MCF-7with estradiol benzoate and a decrease in promoter activity was observed,effect reversed by ICI 182780. We expressed ER?¿ in MDA-MB-231 and had a signaldecrease, suggesting this receptor is responsible of the estrogenic effect. Wedemonstrated that the MEK signaling pathway could be involved in the regulationof ACSL4. We also demonstrated a role of SHP2 on ACSL4 expression and promoteractivity in breast cancer cells.