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: Immunoblot analysis of HIF-1α, HIF-1β, EPAS 1, and ATF-1 in MCF-7 cells following exposure to 0, 0.5, 1, and 21% O2 (normoxia) for 16 h. Blots were stripped and re-probed for β-actin as a loading control; no differences were observed (data not shown).
Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.