The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis

Oncogene. 2008 May 8;27(21):2989-98. doi: 10.1038/sj.onc.1210959. Epub 2007 Dec 3.


Early growth response 3 (Egr3) is a member of a zinc-finger transcription factor subfamily, which we previously found to be strongly upregulated by vascular endothelial growth factor (VEGF)-A in an oligonucleotide microarray screen of endothelial cells. Here, we show that Egr3 is the predominant Egr family member upregulated by VEGF in endothelial cells at 45 min, and that VEGF induced a rapid increase in Egr-dependent transcriptional activation mediated via its major signalling receptor, VEGFR2/KDR, and the protein kinase C (PKC) pathway. VEGF-induced Egr3 gene expression was also mediated in part via a PKC-dependent activation of protein kinase D. Inhibition of Egr3 gene expression by RNA interference was effective in inhibiting basal and VEGF-induced Egr3 gene expression, and it also inhibited VEGF-mediated endothelial cell proliferation, migration and tubulogenesis. These findings indicate that Egr3 has an essential downstream role in VEGF-mediated endothelial functions leading to angiogenesis and may have particular relevance for adult angiogenic processes involved in vascular repair and neovascular disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cell Proliferation
  • Cells, Cultured
  • DNA Primers
  • Early Growth Response Protein 3 / genetics
  • Early Growth Response Protein 3 / physiology*
  • Endothelium, Vascular / cytology
  • Gene Expression Regulation / physiology
  • Humans
  • Neovascularization, Physiologic*
  • Oligonucleotide Array Sequence Analysis
  • Protein Kinase C / metabolism
  • RNA, Small Interfering
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptional Activation
  • Up-Regulation
  • Vascular Endothelial Growth Factor A / physiology*


  • DNA Primers
  • EGR3 protein, human
  • RNA, Small Interfering
  • Vascular Endothelial Growth Factor A
  • Early Growth Response Protein 3
  • protein kinase D
  • Protein Kinase C