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: The above findings and previous reports of the rat VL30 being silent in 5% O2 (Anderson et al, 1989) suggest that the SARE and EPO HRE constructs may be more selective for low levels of oxygen than the PGK-1 construct. We therefore examined the responses of the SARE, EPO HRE and PGK-1-driven reporter constructs to mild hypoxia (4% O2) (Figure 2Figure 2
Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.