Regulation of vascular endothelial growth factor receptor-2 expression in pancreatic cancer cells by Sp proteins

Biochem Biophys Res Commun. 2006 Jun 23;345(1):292-301. doi: 10.1016/j.bbrc.2006.04.111. Epub 2006 May 2.


Vascular endothelial growth factor receptor-2 (VEGFR2/KDR) is an important mediator of angiogenesis, and VEGFR2 mRNA is expressed in several pancreatic cancer cell lines. Deletion analysis of the VEGFR2 promoter in Panc-1, AsPC-1, and MiaPaCa-2 pancreatic cancer cells shows that the proximal region of the promoter is primarily responsible for VEGFR2 expression, and two GC-rich sites at -58 and -44 are critical elements in all three cell lines. Panc-1, AsPC-1, and MiaPaCa-2 cells also express Sp1, Sp3, and Sp4 proteins which bind to the GC-rich region of the VEGFR2 promoter in electrophoretic mobility shift and chromatin immunoprecipitation assays. RNA interference with small inhibitory RNAs for Sp1, Sp3, and Sp4 decreases VEGFR2 mRNA and reporter gene activity in transfection assays, confirming that VEGFR2 expression in pancreatic cancer cells is regulated by Sp proteins. These results suggest that VEGFR2 cannot only be targeted by receptor tyrosine kinase inhibitors but also by drugs that downregulate Sp proteins or block Sp-dependent transactivation.

Publication types

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

MeSH terms

  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism*
  • Sp1 Transcription Factor / metabolism*
  • Sp3 Transcription Factor / metabolism*
  • Sp4 Transcription Factor / metabolism*
  • Transcription Factors / metabolism*
  • Vascular Endothelial Growth Factor Receptor-2 / genetics*


  • SP3 protein, human
  • SP4 protein, human
  • Sp1 Transcription Factor
  • Sp4 Transcription Factor
  • Transcription Factors
  • Sp3 Transcription Factor
  • Vascular Endothelial Growth Factor Receptor-2