Source:http://linkedlifedata.com/resource/pubmed/id/14681724
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
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| pubmed:dateCreated |
2003-12-18
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| pubmed:abstractText |
Adenoviral gene expression that is repressed by p53 in nontransformed cells could provide a tumor-specific gene therapy approach for a large subset of tumors. Adenoviral infection in vivo induces stabilization of p53, which can be utilized for a strategy that includes p53-dependent expression of a transcriptional repressor and a target promoter,which is highly susceptible for transcriptional repression. Therefore, we constructed different versions of CMV-promoters (CMVgal) with binding sites for GAL4-DBD and investigated 11 GAL4-DBD fusion proteins to elucidate the most effective repressor domain to silence CMVgal activity. The transcriptional repressor GAL4-KRAB-A under control of a p53-dependent promoter facilitates strong CMVgal-mediated gene expression specifically in p53 mutant cells by a double-recombinant adenoviral vector (Ad-RGCdR). GAL4-KRAB-A mediates strong transcriptional repression of Ad-RGCdR in p53 wild-type cells, which could be further enhanced by preactivation of p53-signalling following low-dose chemotherapy prior to adenoviral infection. By utilizing p53 signalling involved in chemotherapy and adenoviral infection, more than 99% of Ad-RGCdR gene expression could be repressed in p53 wild-type cells. Controlled gene expression from CMVgal promoters by transcriptional repression utilizing functional p53 signalling thus provides a very effective tool for tumor-specific adenoviral gene therapy.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Repressor Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p53
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jan
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| pubmed:issn |
0929-1903
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
11
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
28-40
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| pubmed:dateRevised |
2009-11-3
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| pubmed:meshHeading |
pubmed-meshheading:14681724-Adenoviridae,
pubmed-meshheading:14681724-Animals,
pubmed-meshheading:14681724-Cell Line, Tumor,
pubmed-meshheading:14681724-Cytomegalovirus,
pubmed-meshheading:14681724-Down-Regulation,
pubmed-meshheading:14681724-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:14681724-Gene Therapy,
pubmed-meshheading:14681724-Genetic Vectors,
pubmed-meshheading:14681724-Humans,
pubmed-meshheading:14681724-Male,
pubmed-meshheading:14681724-Mice,
pubmed-meshheading:14681724-Neoplasms,
pubmed-meshheading:14681724-Organ Specificity,
pubmed-meshheading:14681724-Promoter Regions, Genetic,
pubmed-meshheading:14681724-Recombinant Fusion Proteins,
pubmed-meshheading:14681724-Repressor Proteins,
pubmed-meshheading:14681724-Signal Transduction,
pubmed-meshheading:14681724-Transcription, Genetic,
pubmed-meshheading:14681724-Transcription Factors,
pubmed-meshheading:14681724-Transgenes,
pubmed-meshheading:14681724-Tumor Suppressor Protein p53
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| pubmed:year |
2004
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| pubmed:articleTitle |
Tumor-specific adenoviral gene therapy: transcriptional repression of gene expression by utilizing p53-signal transduction pathways.
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| pubmed:affiliation |
Department of Gastroenterology, Hepatology and Endocrinology, Medical School Hannover, Carl Neuberg Str. 1, 30625 Hannover, Germany.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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