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A role for hypoxia and hypoxia-inducible transcription factors in tumor physiology.
- Source :
- Journal of Molecular Medicine; Sep2002, Vol. 80 Issue 9, p562-575, 14p
- Publication Year :
- 2002
-
Abstract
- Cumulative acquisition of genetic alterations affecting oncogenes or tumor suppressor genes may select for tumor cell clones with enhanced proliferation and survival potential. As a result oxygen and nutrient consumption increases, leading to a tumor microenvironment characterized by low oxygen tension, low glucose levels, and an acidic pH. Hypoxia-inducible transcription factors (HIF) are activated in response to hypoxia, apparently via reduced activity of the recently identified class of 2-oxoglutarate dependent oxygenases, as well as various tumor specific genetic alterations. A widespread HIF activation can be observed in a variety of malignant tumors. The HIF system induces adaptive responses including angiogenesis, glycolysis, and pH regulation which confer increased resistance towards the hostile tumor microenvironment. Apart from protumorigenic the wide-ranging HIF pathway may also have antitumorigenic components, which might, however, be counteracted by specific genetic mechanisms. Thus mounting evidence suggests that the HIF system plays a decisive role in tumor physiology and progression. Moreover, recent insight into this pathway has opened novel and potentially selective therapeutic approaches. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09462716
- Volume :
- 80
- Issue :
- 9
- Database :
- Complementary Index
- Journal :
- Journal of Molecular Medicine
- Publication Type :
- Academic Journal
- Accession number :
- 15735026
- Full Text :
- https://doi.org/10.1007/s00109-002-0355-1