Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia

Berndt Enholm, Karri Paavonen, Ari Ristimäki, Vijay Kumar, Yuji Gunji, Juha Klefstrom, Laura Kivinen, Marikki Laiho, Birgitta Olofsson, Vladimir Joukov, Ulf Eriksson, Kari Alitalo

Research output: Contribution to journalArticle

Abstract

The vascular endothelial growth factor (VEGF) family has recently been expanded by the isolation of two additional growth factors, VEGF-B and VEGF-C. Here we compare the regulation of steady-state levels of VEGF, VEGF-B and VEGF-C mRNAs in cultured cells by a variety of stimuli implicated in angiogenesis and endothelial cell physiology. Hypoxia, Ras oncoprotein and mutant p53 tumor suppressor, which are potent inducers of VEGF mRNA did not increase VEGF-B or VEGF-C mRNA levels. Serum and its component growth factors, platelet-derived growth factor (PDGF) and epidermal growth factor (EGF) as well as transforming growth factor-β (TGF-β) and the tumor promoter phorbol myristate 12,13-acetate (PMA) stimulated VEGF-C, but not VEGF-B mRNA expression. Interestingly, these growth factors and hypoxia simultaneously downregulated the mRNA of another endothelial cell specific ligand, angiopoietin-1. Serum induction of VEGF-C mRNA occurred independently of protein synthesis; with an increase of the mRNA half-life from 3.5 h to 5.5-6 h, whereas VEGF-B mRNA was very stable (T(1/2) > 8 h). Our results reveal that the three VEGF genes are regulated in a strikingly different manner, suggesting that they serve distinct, although perhaps overlapping functions in vivo.

Original languageEnglish (US)
Pages (from-to)2475-2483
Number of pages9
JournalOncogene
Volume14
Issue number20
DOIs
StatePublished - Jul 8 1997
Externally publishedYes

Keywords

  • Angiogenesis
  • Angiopoietin
  • VEGF
  • VEGF-B
  • VEGF-C

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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  • Cite this

    Enholm, B., Paavonen, K., Ristimäki, A., Kumar, V., Gunji, Y., Klefstrom, J., Kivinen, L., Laiho, M., Olofsson, B., Joukov, V., Eriksson, U., & Alitalo, K. (1997). Comparison of VEGF, VEGF-B, VEGF-C and Ang-1 mRNA regulation by serum, growth factors, oncoproteins and hypoxia. Oncogene, 14(20), 2475-2483. https://doi.org/10.1038/sj.onc.1201090