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

Kelly J. Higgins, Maen Abdelrahim, Shengxi Liu, Kyungsil Yoon, Stephen Safe

Research output: Contribution to journalArticle

63 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)292-301
Number of pages10
JournalBiochemical and Biophysical Research Communications
Volume345
Issue number1
DOIs
StatePublished - Jun 23 2006

Keywords

  • Angiogenesis
  • Pancreatic
  • Regulation
  • Sp
  • VEGFR2

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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