CAPER-α 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-α on the expression of the VEGF isoforms, tumor growth, and vessel density was analyzed after transfection of TC-71 cells with CAPER-α cDNA or siRNA.


RESULTS
CAPER-α correlated inversely with the VEGF(165) /VEGF(189) mRNA ratio. Up-regulation of CAPER-α resulted in decreased tumor growth, tumor vessel density, and chemotactic activity of the cell's supernatant. CAPER-α expression was regulated by EWS/FLI-1 through a protein-protein interaction.


CONCLUSIONS
Increased VEGF(165) expression is secondary to the down-regulation of CAPER-α by EWS/FLI-1. CAPER-α mediates alternative splicing and controls the shift from VEGF(189) to VEGF(165) .
Division of Pediatrics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Gangxiong
G
Huang
Zhichao
Z
Zhou
Hua
H
Wang
Eugenie S
ES
Kleinerman
D017398:Alternative Splicing; D000818:Animals; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D009687:Nuclear Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion / Q000378:metabolism; D051789:Proto-Oncogene Protein c-fli-1 / Q000378:metabolism; D034802:RNA-Binding Protein EWS / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics*; D012512:Sarcoma, Ewing / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
C106031:EWS-FLI fusion protein; C084105:HCC1 autoantigen; D009687:Nuclear Proteins; D015514:Oncogene Proteins, Fusion; D051789:Proto-Oncogene Protein c-fli-1; D034802:RNA-Binding Protein EWS; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A