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

Cancer. 2012 Apr 15;118(8):2106-16. doi: 10.1002/cncr.26488. Epub 2011 Aug 25.

Abstract

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) .

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alternative Splicing*
  • Animals
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, Nude
  • Neoplasm Transplantation
  • Nuclear Proteins / genetics*
  • Oncogene Proteins, Fusion / metabolism
  • Proto-Oncogene Protein c-fli-1 / metabolism
  • RNA-Binding Protein EWS / metabolism
  • RNA-Binding Proteins / genetics*
  • Sarcoma, Ewing / genetics*
  • Transcription Factors / metabolism
  • Transfection
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • EWS-FLI fusion protein
  • HCC1 autoantigen
  • Nuclear Proteins
  • Oncogene Proteins, Fusion
  • Proto-Oncogene Protein c-fli-1
  • RNA-Binding Protein EWS
  • RNA-Binding Proteins
  • Transcription Factors
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A