Transcriptional upregulation of human cathepsin L by VEGF in glioblastoma cells.
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.
Keerthivasan
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Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi-110029, India. shilpa_aims@yahoo.com
Keerthivasan
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Mittal
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Chauhan
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D001483:Base Sequence; D056668:Cathepsin L; D002403:Cathepsins / Q000096:biosynthesis* / Q000235:genetics; D045744:Cell Line, Tumor; D003546:Cysteine Endopeptidases / Q000096:biosynthesis* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D005909:Glioblastoma; D006801:Humans; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D020218:Response Elements; D015533:Transcriptional Activation; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology*
D042461:Vascular Endothelial Growth Factor A; D002403:Cathepsins; D003546:Cysteine Endopeptidases; C534281:CTSL protein, human; D056668:Cathepsin L