Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.

Tumor hypoxia induces the up-regulation of a gene program associated with angiogenesis, glycolysis, adaptation to pH, and apoptosis via the hypoxia-inducible transcription factors (Hifs) 1 and 2. Disruption of this pathway has been proposed as a cancer therapy. Here, we use short interfering RNAs to...

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Main Authors: Sowter, H, Raval, R, Moore, J, Ratcliffe, P, Harris, A
Format: Journal article
Language:English
Published: 2003
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author Sowter, H
Raval, R
Moore, J
Ratcliffe, P
Harris, A
author_facet Sowter, H
Raval, R
Moore, J
Ratcliffe, P
Harris, A
author_sort Sowter, H
collection OXFORD
description Tumor hypoxia induces the up-regulation of a gene program associated with angiogenesis, glycolysis, adaptation to pH, and apoptosis via the hypoxia-inducible transcription factors (Hifs) 1 and 2. Disruption of this pathway has been proposed as a cancer therapy. Here, we use short interfering RNAs to compare specific inactivation of Hif-1alpha or Hif-2alpha and show markedly different cell type-specific effects on gene expression and cell migration. Remarkably, among a panel of hypoxia-inducible genes, responses were critically dependent on Hif-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent on Hif-2 alpha in renal carcinoma cells.
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spelling oxford-uuid:25d90596-0ae8-4e57-bdbe-92293f4287b12022-03-26T11:57:49ZPredominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:25d90596-0ae8-4e57-bdbe-92293f4287b1EnglishSymplectic Elements at Oxford2003Sowter, HRaval, RMoore, JRatcliffe, PHarris, ATumor hypoxia induces the up-regulation of a gene program associated with angiogenesis, glycolysis, adaptation to pH, and apoptosis via the hypoxia-inducible transcription factors (Hifs) 1 and 2. Disruption of this pathway has been proposed as a cancer therapy. Here, we use short interfering RNAs to compare specific inactivation of Hif-1alpha or Hif-2alpha and show markedly different cell type-specific effects on gene expression and cell migration. Remarkably, among a panel of hypoxia-inducible genes, responses were critically dependent on Hif-1 alpha but not Hif-2 alpha in both endothelial and breast cancer cells but critically dependent on Hif-2 alpha in renal carcinoma cells.
spellingShingle Sowter, H
Raval, R
Moore, J
Ratcliffe, P
Harris, A
Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title_full Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title_fullStr Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title_full_unstemmed Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title_short Predominant role of hypoxia-inducible transcription factor (Hif)-1alpha versus Hif-2alpha in regulation of the transcriptional response to hypoxia.
title_sort predominant role of hypoxia inducible transcription factor hif 1alpha versus hif 2alpha in regulation of the transcriptional response to hypoxia
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AT ravalr predominantroleofhypoxiainducibletranscriptionfactorhif1alphaversushif2alphainregulationofthetranscriptionalresponsetohypoxia
AT moorej predominantroleofhypoxiainducibletranscriptionfactorhif1alphaversushif2alphainregulationofthetranscriptionalresponsetohypoxia
AT ratcliffep predominantroleofhypoxiainducibletranscriptionfactorhif1alphaversushif2alphainregulationofthetranscriptionalresponsetohypoxia
AT harrisa predominantroleofhypoxiainducibletranscriptionfactorhif1alphaversushif2alphainregulationofthetranscriptionalresponsetohypoxia