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Hypoxia induces a cascade of physiological responses that includes glycolysis, erythropoiesis, angiogenesis, changes in adrenergic signal transduction and vascular cellular proliferation. Hypoxia-inducible genes are relevant to growth and behaviour of cancer as well as the adaptation and survival of normal tissues. Hypoxia-inducible factor-1 (HIF-1) is a heterodimeric DNA binding complex composed of two basic-helix-loop-helix PAS-proteins: HIF-1 beta/ARNT (aryl hydrocarbon receptor nuclear translocator), which is constitutively expressed, and HIF-1 alpha, which is not present in normoxic cells but induced under hypoxic conditions. Recently another member of the bHLH-PAS family, EPAS-1 has been reported and shares similar properties with HIF-1 alpha, although it is considered endothelial specific. In addition, the presence of other DNA-binding motifs in the promoter of hypoxia-inducible genes highlight the occurrence of cross-talk between transcription factors in the modulation of hypoxic gene expression. In this review, we present a survey of the hypoxia response pathway and we discuss attempts to use gene therapy activated by the low oxygen environment or by necrotic regions of tumours.

Type

Journal article

Journal

Cancer Metastasis Rev

Publication Date

06/1998

Volume

17

Pages

187 - 194

Keywords

Animals, Cell Hypoxia, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Genetic Therapy, Humans, Hypoxia-Inducible Factor 1, Hypoxia-Inducible Factor 1, alpha Subunit, Neoplasms, Neoplasms, Experimental, Neovascularization, Pathologic, Nuclear Proteins, Signal Transduction, Transcription Factors