Endocan is a VEGF-A and PI3K regulated gene with increased expression in human renal cancer

Exp Cell Res. 2007 Apr 15;313(7):1285-94. doi: 10.1016/j.yexcr.2007.01.021. Epub 2007 Feb 6.

Abstract

An in vitro model of VEGF-A-induced angiogenesis was used to generate transcription profiles of human microvascular endothelial cells. Microarray analysis showed increased transcription of genes known to regulate angiogenesis, but also genes that previously have not been firmly associated with angiogenesis such as endocan, pinin, plakophilin, phosphodiesterase 4B and gelsolin. Increased endocan mRNA levels in response to VEGF-A in endothelial cells and in human renal cancer have previously been reported. We now show increased endocan protein levels in VEGF-A treated endothelial cells and in human renal clear cell carcinoma. Increased protein expression was observed both in tumor cells and in a subset of tumor vessels, while expression in normal kidney tissue was low. VEGF-A seemed to be a specific inducer of endocan transcription since FGF-2, PDGF-BB, HGF/SF and EGF did not alter expression levels. Inhibition of PI3K with LY294002 caused a 12-fold increase in endocan transcription suggesting a repressive function of PI3K. In contrast inhibition of Src or MEK, which are signaling pathways activated by VEGF-A, did not influence basal or VEGF-A-induced endocan levels. In conclusion our study shows that, among angiogenic growth factors, VEGF-A is a specific inducer of endocan transcription which is translated into increased protein levels in VEGF-A treated endothelial cells. Increased endocan protein expression in human renal cancer suggests a role in tumor growth.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Renal Cell / genetics
  • Carcinoma, Renal Cell / metabolism*
  • Cell Differentiation
  • Cell Line
  • Endothelial Cells / drug effects
  • Endothelial Cells / metabolism
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Kidney Neoplasms / genetics
  • Kidney Neoplasms / metabolism*
  • Neoplasm Proteins / metabolism*
  • Neoplasm Proteins / pharmacology
  • Neovascularization, Pathologic / chemically induced
  • Neovascularization, Pathologic / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Phosphatidylinositol 3-Kinases / metabolism*
  • Phosphatidylinositol 3-Kinases / physiology
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteoglycans / metabolism*
  • Proteoglycans / pharmacology
  • Transcription, Genetic
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • ESM1 protein, human
  • Neoplasm Proteins
  • Phosphoinositide-3 Kinase Inhibitors
  • Proteoglycans
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A