Hypoxia modulated gene expression: angiogenesis, metastasis and therapeutic exploitation.
Tumour hypoxia is the result of an imbalance in oxygen supply and demand. It is an adverse prognostic indicator in cancer as it modulates tumour progression and treatment. Many genes controlling tumour biology are oxygen regulated, and new ones are constantly added to the growing list of hypoxia-induced genes. Of specific importance are hypoxia-responsive transcription factors, as they can modulate the expression of numerous different genes. Similarly, growth factors which govern the formation of new blood vessels or which control blood flow are vitally important for both the maintenance of the primary tumour and metastases at distant sites. The purpose of this review is to present an update of selected issues regarding hypoxia-inducible gene expression and how this affects prognosis, angiogenesis and metastasis. It will conclude by discussing gene therapy as one possible means of exploiting tumour hypoxia for the treatment of cancer.
Dachs
G U
GU
Tumour Microcirculation Group, Gray Laboratory Cancer Research Trust, PO Box 100, Mount Vernon Hospital, HA6 2JR, Northwood, UK.
Tozer
G M
GM
D015687:Cell Hypoxia / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics; D016158:Genes, p53 / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D051793:Hypoxia-Inducible Factor 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008222:Lymphokines / Q000235:genetics; D020782:Matrix Metalloproteinases / Q000502:physiology; D009362:Neoplasm Metastasis / Q000235:genetics* / Q000628:therapy; D009363:Neoplasm Proteins / Q000235:genetics; D009369:Neoplasms / Q000098:blood supply* / Q000235:genetics; D009389:Neovascularization, Pathologic; D019001:Nitric Oxide Synthase / Q000502:physiology; D009687:Nuclear Proteins / Q000235:genetics; D014157:Transcription Factors; D014568:Urokinase-Type Plasminogen Activator / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
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; D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase; D014568:Urokinase-Type Plasminogen Activator; D020782:Matrix Metalloproteinases