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Trends Mol Med. 2002;8(4 Suppl):S62-7.

HIF-1 and tumor progression: pathophysiology and therapeutics.

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  • 1Institute of Genetic Medicine, The Johns Hopkins University School of Medicine, 600 N. Wolfe Street, CMSC-1004, Baltimore, MD 21287-3914, USA. gsemenza@jhmi.edu

Abstract

Hypoxia-inducible factor 1 (HIF-1) controls oxygen delivery (via angiogenesis) and metabolic adaptation to hypoxia (via glycolysis). HIF-1 consists of a constitutively expressed HIF-1 beta subunit and an oxygen- and growth-factor-regulated HIF-1 alpha subunit. In xenografts, tumor growth and angiogenesis are correlated with HIF-1 expression. In human cancers, HIF-1 alpha is overexpressed as a result of intratumoral hypoxia and genetic alterations affecting key oncogenes and tumor suppressor genes. HIF-1 alpha overexpression in biopsies of brain, breast, cervical, esophageal, oropharyngeal and ovarian cancers is correlated with treatment failure and mortality. Increased HIF-1 activity promotes tumor progression, and inhibition of HIF-1 could represent a novel approach to cancer therapy.

PMID:
11927290
[PubMed - indexed for MEDLINE]
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