Glycerol-3-Phosphate Acyltranferase-2 Behaves as a Cancer Testis Gene andPromotes Growth and Tumorigenicity of the Breast Cancer MDA-MB-231 CellLine

PELLON MAISON, MAGALI; MONTANARO, MAURO ALDO; LACUNZA, EZEQUIEL; GARCIA FABIANI, MARIA BELEN; SOLER, MERCEDES; CATTANEO, ELIZABETH; QUIROGA, IVANA YOSELI; ABBA, MARTIN; COLEMAN, ROSALIND; GONZALEZ BARO, MARIA DEL ROSARIO

PLOS ONE

PUBLIC LIBRARY SCIENCE

Lugar: San Francisco; Año: 2014 vol. 9

1932-6203

The de novo synthesis of glycerolipids in mammalian cells begins with the acylation ofglycerol-3-phosphate, catalyzed by glycerol-3-phosphate acyltransferase (GPAT).GPAT2 is a mitochondrial isoform primarily expressed in testis under physiologicalconditions. Because it is aberrantly expressed in multiple myeloma, it has beenproposed as a novel cancer testis gene. Using a bioinformatics approach, we foundthat GPAT2 is highly expressed in melanoma, lung, prostate and breast cancer, andwe validated GPAT2 expression at the protein level in breast cancer byimmunohistochemistry. In this case GPAT2 expression correlated with a higherhistological grade. 5-Aza-2´deoxycytidine treatment of human cells lines inducedGPAT2 expression suggesting epigenetic regulation of gene expression. In order toevaluate the contribution of GPAT2 to the tumor phenotype, we silenced its expressionin MDA-MB-231 cells. GPAT2 knockdown diminished cell proliferation, anchorageindependent growth, migration and tumorigenicity, and increased staurosporineinducedapoptosis. In contrast, GPAT2 over-expression increased cell proliferationrate and resistance to staurosporine-induced apoptosis. To understand the functionalrole of GPAT2, we performed a co-expression analysis in mouse and human testis andfound a significant association with semantic terms involved in cell cycle, DNA integritymaintenance, piRNA biogenesis and epigenetic regulation. Overall, these resultsindicate the GPAT2 would be directly associated with the control of cell proliferation. Inconclusion, we confirm GPAT2 as a cancer testis gene and that its expressioncontributes to the tumor phenotype of MDA-MB-231 cells.