Abstract
CDglyTK fusion suicide gene has been well characterized to effectively kill tumor cells. However, the exact mechanism and downstream target genes are not fully understood. In our study, we found that CDglyTK/prodrug treatment works more efficiently in p53 wild-type (HONE1) cells than in p53 mutant (CNE1) cells. We then used adenovirus-mediated gene delivery system to either knockdown or overexpress p53 and its target genes in these cells. Consistent results showed that both p53-PUMA/NOXA/Bcl2-Bax and p53-p21 pathways contribute to the CDglyTK induced tumor cell suppression. Our work for the first time addressed the role of p53 related genes in the CDglyTK/prodrug system.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis
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Apoptosis Regulatory Proteins / genetics
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Apoptosis Regulatory Proteins / metabolism*
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Cell Line, Tumor
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Cyclin-Dependent Kinase Inhibitor p21 / genetics
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Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
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Genes, Transgenic, Suicide*
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Genetic Therapy
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Humans
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Mitochondria / metabolism
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Neoplasms / therapy*
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Prodrugs / therapeutic use
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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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Thymidine Kinase / genetics
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Tumor Suppressor Protein p53 / genetics
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Tumor Suppressor Protein p53 / metabolism*
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bcl-2-Associated X Protein / genetics
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bcl-2-Associated X Protein / metabolism*
Substances
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Apoptosis Regulatory Proteins
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BBC3 protein, human
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CDKN1A protein, human
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Cyclin-Dependent Kinase Inhibitor p21
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PMAIP1 protein, human
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Prodrugs
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Proto-Oncogene Proteins
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Proto-Oncogene Proteins c-bcl-2
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Tumor Suppressor Protein p53
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bcl-2-Associated X Protein
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Thymidine Kinase