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: Mean (±s.e.m.) fold induction (relative to normoxia; top panel), firefly LUC (middle panel) and Renilla LUC (bottom panel) detected in MCF-7 cells following transfection with the pGL3 Promoter vector, or this containing trimerised versions of the SARE, the human EPO HRE, the human ALD HRE or the murine PGK-1 HRE. Cells were exposed to 0, 0.5, 1 or 21% O2 for 16 h. *P<0.05 with respect to the same trimer at 0.5% O2 (unpaired t-test). Pooled data from three experiments are shown.
Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.