Document Detail

Fumarate hydratase deficiency and cancer: activation of hypoxia signaling?
MedLine Citation:
PMID:  17418405     Owner:  NLM     Status:  MEDLINE    
Molecular genetic analysis of hereditary leiomyomatosis and renal cell cancer (HLRCC) unexpectedly revealed germline defects in the gene encoding the Krebs cycle enzyme fumarate hydratase (FH), stimulating great interest in the underlying mechanism of oncogenesis. It has been proposed that the associated accumulation of fumarate competitively inhibits the 2-oxoglutarate-dependent dioxygenases that regulate hypoxia-inducible factor (HIF), thus activating oncogenic hypoxia pathways. In this issue of Cancer Cell, Pollard and colleagues describe a genetic mouse model of FH deficiency that recapitulates aspects of the human disease, including HIF activation and renal cysts, enabling further insights into this unusual cancer syndrome.
Peter J Ratcliffe
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Publication Detail:
Type:  Comment; Journal Article    
Journal Detail:
Title:  Cancer cell     Volume:  11     ISSN:  1535-6108     ISO Abbreviation:  Cancer Cell     Publication Date:  2007 Apr 
Date Detail:
Created Date:  2007-04-09     Completed Date:  2007-05-15     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101130617     Medline TA:  Cancer Cell     Country:  United States    
Other Details:
Languages:  eng     Pagination:  303-5     Citation Subset:  IM    
The Henry Wellcome Building for Molecular Physiology, University of Oxford, Headington Campus, Roosevelt Drive, Oxford OX3 7BN, United Kingdom.
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MeSH Terms
Disease Models, Animal
Fumarate Hydratase / deficiency*,  genetics
Germ-Line Mutation
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
Kidney Neoplasms / enzymology,  etiology*,  genetics
Leiomyomatosis / enzymology,  etiology*,  genetics
Neoplastic Syndromes, Hereditary / enzymology,  etiology,  genetics
Signal Transduction
Reg. No./Substance:
0/Hypoxia-Inducible Factor 1, alpha Subunit; EC Hydratase
Comment On:
Cancer Cell. 2007 Apr;11(4):311-9   [PMID:  17418408 ]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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