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Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1.

Ameri K, Burke B, Lewis CE, Harris AL - Br. J. Cancer (2002)

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.

View Article: PubMed Central - PubMed

Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.

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Mean (±s.e.m) standardised LUC light units (ratio of firefly LUC/Renilla LUC readings) 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, the murine PGK-1 HRE. Cells were exposed to 4 or 21% O2 for 16 h. *P<0.01 with respect to same trimer at 21% O2 (unpaired t-test). Pooled data from three experiments are shown.
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fig2: Mean (±s.e.m) standardised LUC light units (ratio of firefly LUC/Renilla LUC readings) 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, the murine PGK-1 HRE. Cells were exposed to 4 or 21% O2 for 16 h. *P<0.01 with respect to same trimer at 21% O2 (unpaired t-test). Pooled data from three experiments are shown.

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


Regulation of a rat VL30 element in human breast cancer cells in hypoxia and anoxia: role of HIF-1.

Ameri K, Burke B, Lewis CE, Harris AL - Br. J. Cancer (2002)

Mean (±s.e.m) standardised LUC light units (ratio of firefly LUC/Renilla LUC readings) 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, the murine PGK-1 HRE. Cells were exposed to 4 or 21% O2 for 16 h. *P<0.01 with respect to same trimer at 21% O2 (unpaired t-test). Pooled data from three experiments are shown.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376195&req=5

fig2: Mean (±s.e.m) standardised LUC light units (ratio of firefly LUC/Renilla LUC readings) 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, the murine PGK-1 HRE. Cells were exposed to 4 or 21% O2 for 16 h. *P<0.01 with respect to same trimer at 21% O2 (unpaired t-test). Pooled data from three experiments are shown.
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

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.

View Article: PubMed Central - PubMed

Affiliation: Tumour Targeting Group, Division of Genomic Medicine, University of Sheffield Medical School, Beech Hill Road, Sheffield S10 2RX, UK.

Show MeSH
Related in: MedlinePlus