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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
24
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pubmed:dateCreated |
2001-1-11
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pubmed:abstractText |
The transcriptional complex hypoxia-inducible factor-1 (HIF-1) has emerged as an important mediator of gene expression patterns in tumors, although the range of responding genes is still incompletely defined. Here we show that the tumor-associated carbonic anhydrases (CAs) are tightly regulated by this system. Both CA9 and CA12 were strongly induced by hypoxia in a range of tumor cell lines. In renal carcinoma cells that are defective for the von Hippel-Lindau (VHL) tumor suppressor, up-regulation of these CAs is associated with loss of regulation by hypoxia, consistent with the critical function of pVHL in the regulation of HIF-1. Further studies of CA9 defined a HIF-1-dependent hypoxia response element in the minimal promoter and demonstrated that tight regulation by the HIF/pVHL system was reflected in the pattern of CA IX expression within tumors. Generalized up-regulation of CA IX in VHL-associated renal cell carcinoma contrasted with focal perinecrotic expression in a variety of non-VHL-associated tumors. In comparison with vascular endothelial growth factor mRNA, expression of CA IX demonstrated a similar, although more tightly circumscribed, pattern of expression around regions of necrosis and showed substantial although incomplete overlap with activation of the hypoxia marker pimonidazole. These studies define a new class of HIF-1-responsive gene, the activation of which has implications for the understanding of hypoxic tumor metabolism and which may provide endogenous markers for tumor hypoxia.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Carbonic Anhydrases,
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/HIF1A protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Hypoxia-Inducible Factor 1, alpha...,
http://linkedlifedata.com/resource/pubmed/chemical/Lymphokines,
http://linkedlifedata.com/resource/pubmed/chemical/Nitroimidazoles,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Oxygen,
http://linkedlifedata.com/resource/pubmed/chemical/RNA,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Sensitizing Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/pimonidazole
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0008-5472
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pubmed:author |
pubmed-author:BeasleyN JNJ,
pubmed-author:HarrisA LAL,
pubmed-author:MaxwellP HPH,
pubmed-author:PastorekJJ,
pubmed-author:PughC WCW,
pubmed-author:RatcliffeP JPJ,
pubmed-author:SibtainAA,
pubmed-author:TalksK LKL,
pubmed-author:TurleyHH,
pubmed-author:TurnerK JKJ,
pubmed-author:WatsonP HPH,
pubmed-author:WilsonG DGD,
pubmed-author:WykoffC CCC
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
7075-83
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:11156414-Anoxia,
pubmed-meshheading:11156414-Blotting, Western,
pubmed-meshheading:11156414-Carbonic Anhydrases,
pubmed-meshheading:11156414-Carcinoma,
pubmed-meshheading:11156414-Carcinoma, Renal Cell,
pubmed-meshheading:11156414-DNA-Binding Proteins,
pubmed-meshheading:11156414-Endothelial Growth Factors,
pubmed-meshheading:11156414-Genes, Reporter,
pubmed-meshheading:11156414-Humans,
pubmed-meshheading:11156414-Hypoxia-Inducible Factor 1,
pubmed-meshheading:11156414-Hypoxia-Inducible Factor 1, alpha Subunit,
pubmed-meshheading:11156414-Immunoblotting,
pubmed-meshheading:11156414-Immunohistochemistry,
pubmed-meshheading:11156414-In Situ Hybridization,
pubmed-meshheading:11156414-Kidney Neoplasms,
pubmed-meshheading:11156414-Lymphokines,
pubmed-meshheading:11156414-Models, Genetic,
pubmed-meshheading:11156414-Necrosis,
pubmed-meshheading:11156414-Nitroimidazoles,
pubmed-meshheading:11156414-Nuclear Proteins,
pubmed-meshheading:11156414-Oxygen,
pubmed-meshheading:11156414-Plasmids,
pubmed-meshheading:11156414-Promoter Regions, Genetic,
pubmed-meshheading:11156414-RNA,
pubmed-meshheading:11156414-RNA, Messenger,
pubmed-meshheading:11156414-Radiation-Sensitizing Agents,
pubmed-meshheading:11156414-Skin Neoplasms,
pubmed-meshheading:11156414-Transcription Factors,
pubmed-meshheading:11156414-Tumor Cells, Cultured,
pubmed-meshheading:11156414-Up-Regulation,
pubmed-meshheading:11156414-Urinary Bladder Neoplasms,
pubmed-meshheading:11156414-Vascular Endothelial Growth Factor A,
pubmed-meshheading:11156414-Vascular Endothelial Growth Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Hypoxia-inducible expression of tumor-associated carbonic anhydrases.
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pubmed:affiliation |
Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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