Source:http://linkedlifedata.com/resource/pubmed/id/16380088
Switch to
Predicate | Object |
---|---|
rdf:type | |
lifeskim:mentions | |
pubmed:issue |
2
|
pubmed:dateCreated |
2006-1-3
|
pubmed:abstractText |
The high mutation rates of retroviruses are a potential problem with retroviral vectors. We studied the mutation rates and spectra of p53 sequences transduced with a retroviral vector in a cancer gene therapy model. When p53-deficient H358 non-small cell lung cancer cells were treated with a retroviral vector carrying normal p53 cDNA, most of transduced cells were killed by apoptosis. However, a small number of clones escaped p53-mediated apoptosis. We examined the p53 cDNA structure in these resistant clones. PCR-based analysis showed that 88/102 clones had detectable mutations in p53, including gross rearrangements, deletions/insertions, and base substitutions. To study the mutation rate of the p53 sequence in all transduced clones, the retroviral vector containing the non-functional p53 gene and the Neo-resistant marker gene was introduced into H358 cells. Only one of 95 isolated clones showed a base substitution. These results indicate that the mutation rate of p53 is not particularly high, but there is a significant risk that cancer cells will resist p53 gene therapy as a result of retroviral replication errors.
|
pubmed:language |
eng
|
pubmed:journal | |
pubmed:citationSubset |
IM
|
pubmed:chemical | |
pubmed:status |
MEDLINE
|
pubmed:month |
Feb
|
pubmed:issn |
0006-291X
|
pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
10
|
pubmed:volume |
340
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
|
pubmed:pagination |
567-72
|
pubmed:dateRevised |
2006-11-15
|
pubmed:meshHeading |
pubmed-meshheading:16380088-Animals,
pubmed-meshheading:16380088-Base Sequence,
pubmed-meshheading:16380088-Blotting, Southern,
pubmed-meshheading:16380088-Carcinoma, Non-Small-Cell Lung,
pubmed-meshheading:16380088-Cell Line, Tumor,
pubmed-meshheading:16380088-DNA, Complementary,
pubmed-meshheading:16380088-Gene Transfer Techniques,
pubmed-meshheading:16380088-Genetic Vectors,
pubmed-meshheading:16380088-Humans,
pubmed-meshheading:16380088-Mice,
pubmed-meshheading:16380088-Mutation,
pubmed-meshheading:16380088-NIH 3T3 Cells,
pubmed-meshheading:16380088-Retroviridae,
pubmed-meshheading:16380088-Tumor Suppressor Protein p53
|
pubmed:year |
2006
|
pubmed:articleTitle |
Mutations in p53 cDNA sequence introduced by retroviral vector.
|
pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8602, Japan.
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|