Transcriptional upregulation of human cathepsin L by VEGF in glioblastoma cells

Gene. 2007 Sep 15;399(2):129-36. doi: 10.1016/j.gene.2007.05.002. Epub 2007 May 13.


The role of vascular endothelial growth factor (VEGF) on cathepsin L expression was investigated in human glioblastoma cells (U87MG). Our results demonstrate the transcriptional upregulation of cathepsin L expression by VEGF. Transient transfection of U87MG cells with VEGF expression vector significantly increased cathepsin L activity. These results were further corroborated by a parallel increase in the mRNA levels and promoter activity of cathepsin L by VEGF. By deletion analysis, we identified a 47 base pair VEGF response element (VRE) in human cathepsin L promoter. Site directed mutagenesis studies demonstrated that both SP-1 and AP-4 motifs present in this region contribute to VEGF responsiveness. These results prove for the first time that over-expression of VEGF in human glioblastoma cells induces cathepsin L expression at the transcriptional level. This mechanism could be involved in the enhanced tumorogenic potential of these cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cathepsin L
  • Cathepsins / biosynthesis*
  • Cathepsins / genetics
  • Cell Line, Tumor
  • Cysteine Endopeptidases / biosynthesis*
  • Cysteine Endopeptidases / genetics
  • Gene Expression Regulation, Neoplastic
  • Glioblastoma
  • Humans
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Response Elements
  • Transcriptional Activation*
  • Up-Regulation*
  • Vascular Endothelial Growth Factor A / physiology*


  • Vascular Endothelial Growth Factor A
  • Cathepsins
  • Cysteine Endopeptidases
  • CTSL protein, human
  • Cathepsin L