TRANSCRIPTIONAL REGULATION OF ACYL-COA SYNTHETASE 4 (ACSL4) IN HUMAN BREAST CANCER CELLS

DATTILO MELINA; LOPEZ PAULA; CASTILLO ANA FERNANDA; ORLANDO ULISES; CORNEJO MACIEL, FABIANA; PODESTA, ERNESTO J; MALOBERTI PAULA

Rosario

Congreso; L Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2014

ACSL4 over-expression correlates with tumor progression and we have demonstrated its functional role in human breast cancer cells, describing that promotes tumor aggressiveness. However the regulation of ACSL4 expression remains unclear. For that purpose we amplified the ACSL4 promoter in order to identify the regulatory mechanisms that are involved in the over-expression of this enzyme in breast cancer cells. Using human genomic DNA, we amplified a 1.7 kb fragment of the ACSL4 promoter containing most of exon 1 and it was subcloned in pNL1.1 vector. We also produced two other constructions by partial deletion of the 5 ´or 3´ ends of the cloned promoter. The constructions were transfected in MCF-7 and MDA-MB 231 cells. We show that there is an element in the 5´ region that negatively regulates the promoter activity in both cell lines. On the other hand the 3´ deletion significantly decreases the activity of the promoter only in MDA-MB-231 cells. We interpret that this region could be responsible for the over-expression of ACSL4 in the more aggressive breast cancer cell line. An inhibitor of histone deacetylase enhances the transcription of ACSL4 on both cell lines while an inhibitor of DNA methylation increases the ACSL4 expression only in MDA-MB-231. Furthermore we demonstrated that JNK and p38 are involved in the regulation of ACSL4 transcription in these cells.