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  • Oncogenomics
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The ternary complex factor Net/Elk-3 participates in the transcriptional response to hypoxia and regulates HIF-1α

Oncogene volume 27, pages 1333–1341 (2008)Cite this article

Abstract

The ternary complex factor Net/Elk3 is downregulated in hypoxia and participates in the induction by hypoxia of several genes, including c-fos, vascular endothelial growth factor and egr-1. However, the global role of Net in hypoxia remains to be elucidated. We have identified, in a large-scale analysis of RNA expression using microarrays, more than 370 genes that are regulated by Net in hypoxia. In order to gain insights into the role of Net in hypoxia, we have analysed in parallel the genes regulated by HIF-1α, the classical factor involved in the response to hypoxia. We identified about 190 genes that are regulated by HIF-1α in hypoxia. Surprisingly, when we compare the genes induced by hypoxia that require either Net or HIF-1α, the majority are the same (75%), suggesting that the functions of both factors are closely linked. Interestingly, in hypoxia, Net regulates the expression of several genes known to control HIF-1α stability, including PHD2, PHD3 and Siah2, suggesting that Net regulates the stability of HIF-1α. We found that inhibition of Net by RNAi leads to decreased HIF-1α expression at the protein level in hypoxia. These results indicate that Net participates in the transcriptional response to hypoxia by regulation of HIF-1α protein stability.

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Acknowledgements

We thank the DNA microarray platform, and above all Christine Bole-Feysot, Bernard Jost, Doulaye Dembele, Philippe Kastner, for their expert, professional and friendly help, the Wasylyk laboratory members for support and encouragement and the IGBMC core facilities. CG received fellowships from the Ministere de la Recherche et Technologie, the Association pour la Recherche contre le Cancer and the Regional Council of Alsace. HD and CG received a fellowship from the Ministere de la Recherche et Technologie. The Wasylyk laboratory is financially supported by the Association pour la Recherche contre le Cancer, the Ligue Nationale Française contre le Cancer (Equipe labellisee), (the Ligue Regionale (Bas-Rhin) contre le Cancer and the Ligue Regionale (Haut-Rhin) contre le Cancer), the Centre National de la Recherche Scientifique, the Institut National de la Sante et de la Recherche Medicale, the EU (FP5 Procure project QLK6-2000–00159 and FP6 Prima project #504587), AICR (05–390) and, as part of the Cancéropôle Grand-Est, by INCa and the Ministry of Research and Higher Education (the Axe IV and DKFZ-CGE projects).

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  1. C Gross and H Dubois-Pot: These authors contributed equally to this work.

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  1. Institut de Génétique et de Biologie Moléculaire et Cellulaire, CNRS/INSERM/ULP, Illkirch Cedex, France

    C Gross, H Dubois-Pot & B Wasylyk

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  1. C Gross
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Correspondence to B Wasylyk.

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

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Gross, C., Dubois-Pot, H. & Wasylyk, B. The ternary complex factor Net/Elk-3 participates in the transcriptional response to hypoxia and regulates HIF-1α. Oncogene 27, 1333–1341 (2008). https://doi.org/10.1038/sj.onc.1210736

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