Document Detail


Tumor hypoxia and cancer progression.
MedLine Citation:
PMID:  16002209     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Aerobic life consumes oxygen for efficient production of high energy compounds. The ability to sense and respond to changes in oxygen partial pressure represents a fundamental property to assure the cellular oxygen supply to be within a narrow range that balances the risks of oxidative damage vs. oxygen deficiency. The discovery of hypoxia-inducible factor-1 (HIF-1) allowed the identification of molecular mechanisms by which changes in oxygenation are transduced to adequate intracellular adaptive responses. It became apparent that hypoxia can initiate cell demise by apoptosis/necrosis but also prevent cell death by provoking adaptive responses that, in turn, facilitate cell proliferation or angiogenesis, thus contributing to tumor progression. Considering that activation of HIF-1 provokes pro-survival as well as pro-death decisions under hypoxia, it will be crucial to understand decision making processes in regulating cell death, adaptation and chemoresistance. Likely, secondary stressors such as pH changes, i.e. acidosis, and the context of genetic alterations will shape the role of HIF-1 to affect susceptibility of cells to undergo hypoxia-induced cell death or to allow adaptation and progression towards malignancy. Understanding the mechanisms by which HIF-1 affects the expression and/or function of key apoptotic regulators such as Bcl-2 family members or p53 will help to uncover how HIF-1 induces cell death and the manner in which cells can overcome such signals and thus determine which of its Janus faces prevail.
Authors:
Jie Zhou; Tobias Schmid; Steffen Schnitzer; Bernhard Brüne
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Review     Date:  2005-07-05
Journal Detail:
Title:  Cancer letters     Volume:  237     ISSN:  0304-3835     ISO Abbreviation:  Cancer Lett.     Publication Date:  2006 Jun 
Date Detail:
Created Date:  2006-05-22     Completed Date:  2006-07-26     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  7600053     Medline TA:  Cancer Lett     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  10-21     Citation Subset:  IM    
Affiliation:
Institute of Biochemistry I, Faculty of Medicine, Johann Wolfgang Goethe-University, Theodor-Stern-Kai 7, 60590 Frankfurt, Germany.
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MeSH Terms
Descriptor/Qualifier:
Angiogenic Proteins / genetics,  metabolism
Animals
Apoptosis / genetics*
Aryl Hydrocarbon Receptor Nuclear Translocator / metabolism
Cell Hypoxia / genetics*
Cell Proliferation
Disease Progression
Drug Resistance, Neoplasm / genetics
Gene Expression Regulation, Neoplastic*
Humans
Hypoxia-Inducible Factor 1, alpha Subunit / metabolism
Membrane Proteins / genetics,  metabolism
Neoplasms / blood supply,  genetics*,  metabolism
Neovascularization, Pathologic / genetics,  metabolism
Proto-Oncogene Proteins / genetics,  metabolism
Tumor Suppressor Protein p53 / genetics,  metabolism
Tumor Suppressor Proteins / genetics,  metabolism
Chemical
Reg. No./Substance:
0/Angiogenic Proteins; 0/BNIP3 protein, human; 0/BNIP3L protein, human; 0/Hypoxia-Inducible Factor 1, alpha Subunit; 0/Membrane Proteins; 0/Proto-Oncogene Proteins; 0/Tumor Suppressor Protein p53; 0/Tumor Suppressor Proteins; 138391-32-9/Aryl Hydrocarbon Receptor Nuclear Translocator

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


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