Abstract
Transcriptional promoters responsive to low doses of X-irradiation may be useful in developing a new strategy in gene therapy combined with conventional radiotherapy. The retrovirus-mediated gene trap screening identified c-IAP2 as one of genes possessing such promoters. The analysis of the cis-elements responsive to X-irradiation in c-IAP2 promoter revealed that the NF-kappaB binding sites were necessary and sufficient for the X-ray-responsiveness. We constructed the plasmid p4NFB-BAX, which had four tandem repeats of the NF-kappaB binding sites of c-IAP2 promoter (4NFB) and a suicide gene BAX under the control of 4NFB. The human tumor cells transfected with p4NFB-BAX significantly reduced the number of cells that survived 2 Gy irradiation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma
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Apoptosis*
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Binding Sites
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Blotting, Western
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Cell Death / radiation effects
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Genes, Reporter
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Humans
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Inhibitor of Apoptosis Proteins
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Luciferases / metabolism
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NF-kappa B / genetics
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NF-kappa B / metabolism*
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Promoter Regions, Genetic
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Protein Binding
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Proteins / genetics
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Proteins / metabolism*
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Proto-Oncogene Proteins / genetics*
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Proto-Oncogene Proteins / metabolism
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Proto-Oncogene Proteins c-bcl-2 / genetics*
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Proto-Oncogene Proteins c-bcl-2 / metabolism
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Sensitivity and Specificity
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Tumor Cells, Cultured
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X-Rays
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bcl-2-Associated X Protein
Substances
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BAX protein, human
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Inhibitor of Apoptosis Proteins
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NF-kappa B
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Proteins
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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bcl-2-Associated X Protein
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Luciferases