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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
1997-2-11
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pubmed:abstractText |
The high point mutation rate of replication error-prone (RER+) cells could theoretically lead to inactivation of the p53 gene by polyclonal mutations, which might explain the conflicting results that have been published on the p53 status of RER+ colon cancers. To address this issue, we tested the p53 status of 21 human colorectal cancer cell lines, including four showing microsatellite instability (RER+ phenotype). Denaturing gradient gel electrophoresis (DGGE) followed by sequencing showed that all four RER+ cell lines were wild type for p53 while 15 of the 17 RER- cell lines contained p53 mutations (P=0.001). Eight cell lines (four RER+ and four RER-) were analysed using three complementary methods to test more rigorously the polyclonal mutation hypothesis. (i) Of 87 single-cell clones (seven to 14 per cell line) examined by DGGE, only those derived from known p53 mutant cell lines showed altered profiles. (ii) Antibody DO-7 stained more than 80% of nuclei from the p53 mutant cell lines, but only 15% of nuclei from the RER+ cell lines. (iii) A yeast functional assay which can simultaneously detect polyclonal mutations at over 500 different sites in the p53 cDNA scored all four RER+ cell lines as containing only transcriptionally active p53. These data thus do not support the polyclonal mutation hypothesis and instead suggest that mismatch repair deficiency provides a p53-independent pathway for development of colorectal cancers.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
|
pubmed:issn |
0950-9232
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pubmed:author | |
pubmed:issnType |
Print
|
pubmed:day |
19
|
pubmed:volume |
13
|
pubmed:owner |
NLM
|
pubmed:authorsComplete |
Y
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pubmed:pagination |
2727-30
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:9000147-Colorectal Neoplasms,
pubmed-meshheading:9000147-DNA Repair,
pubmed-meshheading:9000147-Genes, p53,
pubmed-meshheading:9000147-Humans,
pubmed-meshheading:9000147-Microsatellite Repeats,
pubmed-meshheading:9000147-Point Mutation,
pubmed-meshheading:9000147-Tumor Cells, Cultured
|
pubmed:year |
1996
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pubmed:articleTitle |
Inverse correlation between RER+ status and p53 mutation in colorectal cancer cell lines.
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pubmed:affiliation |
Inserm U 434, Génétique des Tumeurs, Institut Curie, Paris, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|