Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes that are involved in crucial aspects of cancer biology, including angiogenesis, cell survival, glucose metabolism and invasion. Intratumoral hypoxia and genetic alterations can lead to HIF-1alpha overexpression, which has been associated with increased patient mortality in several cancer types. In preclinical studies, inhibition of HIF-1 activity has marked effects on tumour growth. Efforts are underway to identify inhibitors of HIF-1 and to test their efficacy as anticancer therapeutics.

Hypoxia-inducible factor 1 (HIF-1) is an oxygen-regulated transcriptional activator that plays essential roles in mammalian development, physiology and disease pathogenesis. The HIF-1 alpha subunit is subjected to oxygen-dependent ubiquitination and proteasomal degradation that is mediated by the von Hippel-Lindau protein. Interaction of HIF-1 alpha transactivation domains with coactivators is induced by hypoxia. The signal transduction pathway remains enigmatic, but involves generation of reactive oxygen species. Nitric oxide induces HIF-1 alpha under non-hypoxic conditions but inhibits hypoxia-induced HIF-1 alpha expression.

The heterodimeric hypoxia-inducible transcription factor HIF-1 is involved in the oxygen-regulated transcription of several genes including erythropoietin. Cloning and sequencing of the alpha-subunit of mouse HIF-1 cDNA revealed a 90% overall homology to human HIF-l alpha but lack of any similarity in the 5' untranslated region and translational start site. Mouse HIF-1 alpha is encoded by an evolutionary conserved single-copy gene located on chromosome 12. We found a widespread constitutive expression of mouse HIf-1 alpha mRNA which was particularly high in lung and kidney. Despite a strong erythropoietin induction, HIF-1 alpha mRNA concentrations were not upregulated in hypoxic mouse tissues.