title: Vascular endothelial growth factor-induced genes in human umbilical vein endothelial cells: relative roles of KDR and Flt-1 receptors.
abstract: OBJECTIVE
  This study evaluated the relative roles of the vascular endothelial growth factor (VEGF) receptors KDR and Flt-1 in the mediation of altered gene expression elicited by VEGF.
  
  
  RESULTS
  We used mutants of VEGF selective for the KDR and Flt-1 receptors to differentiate gene expression patterns mediated by wild-type VEGF (VEGFwt) in human umbilical vein endothelial cells. RNA was extracted from cells treated for 24 hours with 1 nmol/L of each ligand, and gene expression was monitored by using oligonucleotide arrays (Affymetrix U95A). We report that activation of KDR was sufficient to upregulate all the genes induced by VEGFwt. In contrast, there were no genes selectively upregulated by the Flt-selective mutant. However, high concentrations of the Flt-selective mutant could augment the expression of some genes induced by submaximal concentrations of VEGFwt but not the KDR-selective mutant.
  
  
  CONCLUSIONS
  The binding of VEGF to its receptor, KDR, is necessary and sufficient to induce the gene expression profile induced by this growth factor. Furthermore, in human umbilical vein endothelial cells, the Flt-1 receptor appears to act as a decoy receptor, tempering the response to lower concentrations of VEGF.
authors.affiliation: Department of Cardiovascular Research, Genentech Inc, South San Francisco, Calif, USA.
authors.forename: Suya
authors.initials: S
authors.lastname: Yang
authors.forename: Karen
authors.initials: K
authors.lastname: Toy
authors.forename: Gladys
authors.initials: G
authors.lastname: Ingle
authors.forename: Constance
authors.initials: C
authors.lastname: Zlot
authors.forename: P Mickey
authors.initials: PM
authors.lastname: Williams
authors.forename: Germaine
authors.initials: G
authors.lastname: Fuh
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Abraham
authors.initials: A
authors.lastname: de Vos
authors.forename: Mary E
authors.initials: ME
authors.lastname: Gerritsen
mesh_terms: D002478:Cells, Cultured; D016228:Endothelial Growth Factors / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D008222:Lymphokines / Q000235:genetics / Q000494:pharmacology / Q000502:physiology*; D009154:Mutation / Q000235:genetics / Q000502:physiology; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction / Q000379:methods; D019718:Receptors, CXCR4 / Q000096:biosynthesis; D013997:Time Factors; D014471:Umbilical Veins / Q000737:chemistry* / Q000166:cytology / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D019718:Receptors, CXCR4; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2