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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
16
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pubmed:dateCreated |
2001-8-16
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pubmed:abstractText |
The main inhibitory action of p27, a cyclin-dependent kinase inhibitor (CDKI), arises from its binding with the cyclin E/cyclin-dependent kinase 2 (Cdk2) complex that results in G(1)-S arrest. Degradation of p27 is mediated by phosphorylation of Thr-187 of p27, which follows ubiquitination. In this study, we generated two adenoviruses expressing wild-type p27 (ad-p27wt) and mutant p27 (ad-p27mt), with mutation of Thr-187/Pro-188 (ACGCCC) to Met-187/Ile-188 (ATGATC), which was produced with the belief that mutant p27 would bind cyclin E/CDK2 more stably and show more potent antitumor effects. Ad-p27wt and ad-p27mt expressed p27 proteins that were indistinguishable by anti-p27 antibody. A pulse chase experiment showed that p27mt was more resistant to degradation than p27wt. In human lung cancer cell lines, ad-p27mt showed stronger growth inhibition than ad-p27wt. Both types of ad-p27 induced G(1)-S arrest and apoptosis; however, ad-p27mt induced stronger G(1)-S arrest and apoptosis. Intratumoral injection of ad-p27mt induced partial regression of established tumors and inhibited the growth of human lung cancer xenografts more strongly than ad-p27wt. From these results, we conclude that ad-p27mt has the potential to become a novel and powerful gene therapy tool.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/CDC2-CDC28 Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/CDK2 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cdk2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cdkn1b protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin E,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Poly(ADP-ribose) Polymerases,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Retinoblastoma Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0008-5472
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
61
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
6163-9
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:11507068-Adenoviridae,
pubmed-meshheading:11507068-Animals,
pubmed-meshheading:11507068-Apoptosis,
pubmed-meshheading:11507068-CDC2-CDC28 Kinases,
pubmed-meshheading:11507068-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:11507068-Cell Cycle Proteins,
pubmed-meshheading:11507068-Cell Division,
pubmed-meshheading:11507068-Cyclin E,
pubmed-meshheading:11507068-Cyclin-Dependent Kinase 2,
pubmed-meshheading:11507068-Cyclin-Dependent Kinase Inhibitor p27,
pubmed-meshheading:11507068-Cyclin-Dependent Kinases,
pubmed-meshheading:11507068-DNA Fragmentation,
pubmed-meshheading:11507068-Female,
pubmed-meshheading:11507068-Flow Cytometry,
pubmed-meshheading:11507068-G1 Phase,
pubmed-meshheading:11507068-Gene Therapy,
pubmed-meshheading:11507068-Humans,
pubmed-meshheading:11507068-Lung Neoplasms,
pubmed-meshheading:11507068-Mice,
pubmed-meshheading:11507068-Mice, Inbred BALB C,
pubmed-meshheading:11507068-Mice, Nude,
pubmed-meshheading:11507068-Phosphorylation,
pubmed-meshheading:11507068-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:11507068-Protein-Serine-Threonine Kinases,
pubmed-meshheading:11507068-Retinoblastoma Protein,
pubmed-meshheading:11507068-S Phase,
pubmed-meshheading:11507068-Transduction, Genetic,
pubmed-meshheading:11507068-Tumor Cells, Cultured,
pubmed-meshheading:11507068-Tumor Suppressor Proteins,
pubmed-meshheading:11507068-Xenograft Model Antitumor Assays
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pubmed:year |
2001
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pubmed:articleTitle |
An adenovirus expressing mutant p27 showed more potent antitumor effects than adenovirus-p27 wild type.
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pubmed:affiliation |
Department of Internal Medicine, Seoul National University College of Medicine, Lung Institute of Medical Research Center, Seoul National University, Seoul 110-744, Korea.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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