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Angiopoietin-2 decreases vascular endothelial growth factor expression by modulating HIF-1α levels in gliomas

Oncogene volume 27, pages 1310–1314 (2008)Cite this article

Abstract

Angiogenesis is thought to depend on a perfectly coordinated balance between endogenous-positive and negative regulatory factors. Of these factors, the vascular endothelial growth factor (VEGF) and angiopoietins (Angs) seem to play an essential role. Recently, we reported the expression of the Ang-natural receptor, Tie2, in neoplastic astrocytic cells within gliomas. Because of the VEGF/Ang2 functional partnership together with the presence of Tie2 in gliomas, we hypothesized a role of Ang2 on the modulation of VEGF levels in these tumors. We examined the effect of Ang2 on VEGF expression in a panel of glioma cells, which showed that Ang2 inhibited VEGF expression at both mRNA and protein levels in Tie2-expressing cells, but not in Tie2-negative cells. VEGF promoter analysis showed that Ang2 regulated VEGF expression at the transcriptional level in relation to a decrease in HIF-1α expression and HIF-DNA-binding activity. Tie2 silencing by siRNA rescued the Ang2-mediated downmodulation of VEGF, suggesting an essential role for Tie2 in this regulatory loop. To our knowledge, this is the first report on the role of Ang2/Tie2 in the regulation of HIF-1α/VEGF expression, providing additional evidence of the intrinsic coordination that occurs among these factors during angiogenesis.

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Acknowledgements

We thank Betty L Notzon (Department of Scientific Publications, MD Anderson Cancer Center, Houston, TX, USA) for editorial assistance. This work was supported by grants from NIH (R01-CA83127; CA16672 to Core Facilities at MD Anderson Cancer Center), MD Anderson Cancer Center and Department of Education and Science, Spain (to VA).

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  1. O-H Lee and J Xu: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    O-H Lee, J Xu, J Fueyo, M M Alonso, D Liu, V Martin, H Jiang, Y Piao, T J Liu & C Gomez-Manzano

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  1. O-H Lee
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  2. J Xu
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  3. J Fueyo
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  4. M M Alonso
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  7. H Jiang
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  8. Y Piao
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  10. C Gomez-Manzano
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Correspondence to C Gomez-Manzano.

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Supplementary Information accompanies the paper on the Oncogene website (http://www.nature.com/onc).

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Lee, OH., Xu, J., Fueyo, J. et al. Angiopoietin-2 decreases vascular endothelial growth factor expression by modulating HIF-1α levels in gliomas. Oncogene 27, 1310–1314 (2008). https://doi.org/10.1038/sj.onc.1210731

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