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

Oncogene volume 27, pages 2989–2998 (2008)Cite this article

Abstract

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.

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Acknowledgements

This work was funded by British Heart Foundation Programme Grant RG/06/003/21131 and Ark Therapeutics Ltd.

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Authors and Affiliations

  1. Department of Medicine, BHF Laboratories, University College London, London, UK

    D Liu, I Evans, G Britton & I Zachary

  2. Department of Medicine, Ark Therapeutics Ltd, University College London, London, UK

    D Liu

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  1. D Liu
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  2. I Evans
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  3. G Britton
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Correspondence to I Zachary.

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Liu, D., Evans, I., Britton, G. et al. The zinc-finger transcription factor, early growth response 3, mediates VEGF-induced angiogenesis. Oncogene 27, 2989–2998 (2008). https://doi.org/10.1038/sj.onc.1210959

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