CAPER-a alternative splicing regulates the expression of vascular endothelial growth factor165 in Ewing sarcoma cells

BACKGROUND: TC-71 Ewing sarcoma cells overexpress vascular endothelial growth factor (VEGF) with a shift from the 189 to the 165 isoform. METHODS: The effect of CAPER-a on the expression of the VEGF isoforms, tumor growth, and vessel density was analyzed after transfection of TC-71 cells with CAPER-a cDNA or siRNA. RESULTS: CAPER-a correlated inversely with the VEGF165/VEGF189 mRNA ratio. Up-regulation of CAPER-a resulted in decreased tumor growth, tumor vessel density, and chemotactic activity of the cell's supernatant. CAPER-a expression was regulated by EWS/FLI-1 through a protein-protein interaction. CONCLUSIONS: Increased VEGF165 expression is secondary to the down-regulation of CAPER-a by EWS/FLI-1. CAPER-a mediates alternative splicing and controls the shift from VEGF189 to VEGF165. Cancer 2012; 118: 2106-16. (C) 2011 American Cancer Society.