Molecular consequences of GPAT2 knock-down in breast cancer cells

LACUNZA E; GUILLOU H; MONTANARO MA; SOLER SB; CATTÁNEO ER; GONZALEZ-BARO MR

Cordoba

Congreso; LII Reunión Anual de la Sociedad Argentina de Investigación Bioquímica y Biología Molecular (SAIB); 2016

SAIB

GPAT2, aglycerol-3P-acyltransferase isoform, is mainly expressed in pachytene spermatocytesand also highly expressed in certain tumor cells and tissues. We showed thatGPAT2 expression promotes the tumorigenic phenotype of MDA-MB-231 cells, as itsexpression correlates to higher proliferation rate, lower apoptosis, andincreased tumorigenic behavior, among others. To determine which genes andmolecular pathways could be modified by GPAT2 in MDA-MB-231 cells we performeda transcriptomic analysis using an Agilent SurePrint G3 Human Gene Expression8x60K v2 Microarray of GPAT2 silenced and control MDA cells. After filteringoff for a FC>2 and p value<0.01, we found 616 differentially expressedgenes (DEG; 326 up- and 290 down-regulated). Their functional enrichmentanalysis showed several molecular pathways and cellular processes affected byGPAT2 silencing. We focused on cancer-related pathways, particularly on WNT/Ca2+,which is controversially considered as a tumor inductor or a tumor suppressor pathway,depending on the tissue and other conditions. In our model, several genesbelonging to this pathway were significantly down-regulated upon silencing, ascribingto the Wnt/Ca2+ signaling the role of inductor rather than tumor suppressor.Further studies are needed to connectGPAT2 and WNT/Ca2+, and to establish the impact of GPAT2 silencing on othercancer related genes.