Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1.
Bottom Line: Novel approaches to cancer gene therapy currently exploit tumour hypoxia to achieve transcriptional targeting using oxygen-regulated enhancer elements called hypoxia response elements.Mutational analysis demonstrated that the base immediately 5' to this modulates the anoxic/hypoxic induction of the secondary anoxia response element, such that TACGTG>GACGTG>CACGTG.A similar correlation was found for erythropoietin, phosphoglycerate kinase 1, and aldolase hypoxia response elements, which contain these respective 5' flanking bases.
Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.Show MeSH
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Mentions: Low levels of HIF-1α and HIF-1β were detectable in normoxic MCF-7 nuclear extracts. No HIF-2α (EPAS 1) was detected in normoxia. Levels of all three of these proteins increased markedly in hypoxia (1% and 0.5% O2) and anoxia (Figure 5Figure 5
Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.