The molecular response of mammalian cells to hypoxia and the potential for exploitation in cancer therapy.
In this review, reports of the increased expression of selected genes in response to hypoxia have been summarised. The best studied mammalian hypoxia response systems are those of the erythropoietin (Epo) and the vascular endothelial growth factor (VEGF) genes, which will be described in some detail. Other genes discussed here include those encoding growth factors, cytokines, transcription factors, metabolic enzymes and DNA repair enzymes. Short DNA sequences (hypoxia response elements) governing the increased gene expression in response to hypoxia have been discovered in the vicinity of most of these genes. The review will end by analysing the possibility of exploiting tumour hypoxia via the use of hypoxia response elements for gene therapy of cancer.
Dachs
G U
GU
Medical Research Council, Harwell, Didcot, UK.
Stratford
I J
IJ
D000818:Animals; D015687:Cell Hypoxia; D016207:Cytokines / Q000096:biosynthesis; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000096:biosynthesis; D016228:Endothelial Growth Factors / Q000096:biosynthesis; D004921:Erythropoietin / Q000096:biosynthesis / Q000235:genetics; D015316:Genetic Therapy; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines / Q000096:biosynthesis; D009369:Neoplasms / Q000628:therapy*; D009687:Nuclear Proteins / Q000096:biosynthesis; D014157:Transcription Factors / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
D016207:Cytokines; D004268:DNA-Binding Proteins; D016228:Endothelial Growth Factors; C497442:HIF1A protein, human; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D004921:Erythropoietin