TRANSCRIPTOMIC LANDSCAPE REGULATED BY ACYLCOA SYNTHETASE4 (ACSL4) EXPRESSION IN BREAST CANCER CELLS

ORLANDO, ULISES; DATTILO, MELINA; CASTILLO, ANA FERNANDA; MELE, PABLO; SOLANO, ANGELA; MALOBERTI, PAULA; PODESTÁ, ERNESTO J

Buenos Aires

Congreso; Molecular mechanisms in cell signaling and gene expression Argentine Society for Biochemistry and Molecular Biology scientific meeting ?SAIB 2013?; 2013

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

ACSL4, an enzyme that esterifies arachidonic acid (AA) into arachidonoyl-CoA, is increased in breast, colon and hepatocellular carcinomas. Previously we showed that the transfection of breast cancer MCF-7 cells with ACSL4 cDNA (MCF-7 ACSL4 cells) confers them a highly aggressive phenotype. ACSL4 overexpression increases 5-lipooxygenase (5-LOX) and cyclooxygenase-2 (COX- 2) metabolism of AA. Treatment of MDA-MB-231 tumor xenografts with a combination of ACSL4, 5-LOX and COX-2 inhibitors reduced tumor growth in doses that were ineffective when used alone. Thus ACSL4 is a potential therapeutic target for tumor formation. Therefore, the aim of this study was to identify the genetic elements regulated by ACSL4 expression. Applying a massively mRNA sequencing approach to MCF-7 and MCF-7 ACSL4 cells and employing the TopHat and Cufflinks software analysis, we detected 182 differentially expressed loci with p < 0.05. Within differentially expressed genes, DNMT1, HDAC, IL20, WNT6, RBL2/p130 and TWIST-1 are genes related to cell aggressiveness regulation and to expression regulation of estrogen receptor and COX-2, targets of ACSL4. The high number of differentially expressed genes demonstrates quite effectively that cell aggressivity regulation by ACSL4 is not through changes in an individual molecule or pathway, but it is the result of global changes in gene expression.