Role of Glycerol-3-Phosphate Acyltransferase 2 (GPAT2) in Cell Proliferation and Survival

MONTANARO, M.A.; SOLER-GERINO, M.; GARCIA FABIANI, M.B.; CATTANEO, E.R.; LACUNZA, E.; ABBA, M.; GONZALEZ BARO, M.R.; PELLON-MAISON, M.

Mendoza

Congreso; XLVII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2012

SAIB

The limiting step for glycerolipid biosynthesis is the acylation of glycerol-3-phophate catalysed by glycerol-3-phosphate acyltransferase (GPAT).Although its expression seems to be restricted to very few cell types, in silico analysis showed that GPAT2 could be expressed in breast infiltrating carcinomas. For its validation, qPCR was performed on different cell lines and normal or neoplastic human mammary samples. MDA-MB 231 was the only cell line able to express GPAT2. Also, GPAT2 protein expression by IHC in an independent group of carcinomas (n=35) and normal (n=6) samples showed that GPAT2 protein is not detected in normal tissues, whereas 37% of tumours showed a positive reaction. Protein expression significantly correlated with histological grading (p=0.02).A stable GPAT2 KO MDA cell line, with only 5% of GPAT2 expression had 50% lower cell growing rate on MTT growing curve assays. On the other hand, a stable 10-fold GPAT2 overexpression in MDA cells was able to increase the cell growing rate by 100%.By TUNEL assay, GPAT2 overexpressing cells presented less apoptosis after 2h of 1 µM stauroporine treatment, compared to its control (37% vs 44% p<0.01). With an incubation of 5h, 95% of control cells showed apoptotic traits whereas only 77% of GPAT2 overexpressing cells was affected, p<0.001.Conclusion: the activity of GPAT2 is able to modify cell proliferation and survival.