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J Mol Med (Berl). 2002 Sep;80(9):562-75. Epub 2002 Jun 21.

A role for hypoxia and hypoxia-inducible transcription factors in tumor physiology.

Author information

1
Edinger Institute, Johann Wolfgang Goethe University, Deutschordenstrasse 46, 60528 Frankfurt, Germany. till.acker@kgu.de

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.

PMID:
12226738
DOI:
10.1007/s00109-002-0355-1
[Indexed for MEDLINE]

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