GPAT2 expression influences arachidonic acid dynamics in the breast adenocarcinoma cell line MDA-MB-231

GARCIA FABIANI MARIA BELEN; CATTANEO, ELIZABETH; GONZALEZ BARO, MARIA DEL ROSARIO; MONTANARO, MAURO ALDO

Snowmass, CO

Congreso; FASEB Summer Research Conference; 2016

Federation of American Societies for Experimental Biology

Glycerol-3-phosphate acyltransferases (GPATs) catalyze the first step in the de novo glycerolipid biosynthesis. GPAT2 has been firstly characterized as an acyltransferase, although its enzymatic activity remains elusive. We have previously demonstrated that arachidonoyl-CoA is its preferred substrate for glycerolipid synthesis. Arachidonic acid (AA) turnover is known to be implicated in mammalian cell survival and proliferation because high levels of AA induce apoptosis, whereas metabolic pathways that diminish the content of unesterified AA may prevent it. Using RNAi technology, we have silenced GPAT2 in breast cancer derived MDA-MB-231 cells, which endogenously express high levels of GPAT2. We have demonstrated that GPAT2 expression in this cell line contributed to the tumoral phenotype. To figure out the molecular mechanisms involved in GPAT2-triggered tumorigenesis we studied the effect of AA on cell proliferation and survival in different GPAT2 expression contexts. We observed that 100 µM AA for 2 days decreased MDA-SH (GPAT2-silenced) cell proliferation rate compared to MDA-SCR (control) cells. To establish whether this effect was a consequence of an activation of the apoptotic pathway, we treated MDA-SH and MDA-SCR cells with 100 µM AA for 2 days and observed an increase in the percentage of apoptotic MDA-SH cells compared to control cells. To get an insight into the fate of AA in the absence of GPAT2 expression, we studied the expression of genes that are involved in AA utilization such as AGPAT11, MBOAT5, MBOAT7, AKR1C3, ALOX5, EPHX2, and PTGS1. Our results clearly link GPAT2 with AA and apoptosis, and provide information about the molecular mechanisms through which GPAT2 might contribute to the tumoral phenotype.Funding: CONICET PIP0310 and ANPCyT PICT3214, Argentina.