| pubmed-article:11259619 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C0021467 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C0079419 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C1511681 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C1704259 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C1155291 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C0021469 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C1705987 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C0049065 | lld:lifeskim |
| pubmed-article:11259619 | lifeskim:mentions | umls-concept:C1879547 | lld:lifeskim |
| pubmed-article:11259619 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:11259619 | pubmed:dateCreated | 2001-3-22 | lld:pubmed |
| pubmed-article:11259619 | pubmed:abstractText | Transcriptional silencing of tumor suppressor genes by DNA methylation occurs in cancer cell lines and in human tumors. This has led to the pursuit of DNA methyltransferase inhibition as a drug target. 5-Aza-2'-deoxycytidine [5-aza-CdR (decitabine)], a potent inhibitor of DNA methyltransferase, is a drug currently in clinical trials for the treatment of solid tumors and leukemia. The efficacy of 5-aza-CdR may be related to the induction of methylation-silenced tumor suppressor genes, genomic hypomethylation, and/or enzyme-DNA adduct formation. Here, we test the hypothesis that 5-aza-CdR treatment is perceived as DNA damage, as assessed by the activation of the tumor suppressor p53. We show that 1) colon tumor cell lines expressing wild-type p53 are more sensitive to 5-aza-CdR mediated growth arrest and cytotoxicity; 2) the response to 5-aza-CdR treatment includes the induction and activation of wild-type but not mutant p53 protein; and 3) the induction of the downstream p53 target gene p21 is partially p53-dependent. The induction of p53 protein after 5-aza-CdR treatment did not correlate with an increase in p53 transcripts, indicating that hypomethylation at the p53 promoter does not account for the p53 response. It is relevant that 5-aza-CdR has shown the greatest promise in clinical trials for the treatment of chronic myelogenous leukemia, a malignancy in which functional p53 is often retained. Our data raise the hypothesis that p53 activation may contribute to the clinical efficacy and/or toxicity of 5-aza-CdR. | lld:pubmed |
| pubmed-article:11259619 | pubmed:language | eng | lld:pubmed |
| pubmed-article:11259619 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259619 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:11259619 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11259619 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:11259619 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:11259619 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:11259619 | pubmed:month | Apr | lld:pubmed |
| pubmed-article:11259619 | pubmed:issn | 0026-895X | lld:pubmed |
| pubmed-article:11259619 | pubmed:author | pubmed-author:JonesD ADA | lld:pubmed |
| pubmed-article:11259619 | pubmed:author | pubmed-author:MooreB CBC | lld:pubmed |
| pubmed-article:11259619 | pubmed:author | pubmed-author:KarpfA RAR | lld:pubmed |
| pubmed-article:11259619 | pubmed:author | pubmed-author:RirieT OTO | lld:pubmed |
| pubmed-article:11259619 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:11259619 | pubmed:volume | 59 | lld:pubmed |
| pubmed-article:11259619 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:11259619 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:11259619 | pubmed:pagination | 751-7 | lld:pubmed |
| pubmed-article:11259619 | pubmed:dateRevised | 2006-5-5 | lld:pubmed |
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| pubmed-article:11259619 | pubmed:meshHeading | pubmed-meshheading:11259619... | lld:pubmed |
| pubmed-article:11259619 | pubmed:year | 2001 | lld:pubmed |
| pubmed-article:11259619 | pubmed:articleTitle | Activation of the p53 DNA damage response pathway after inhibition of DNA methyltransferase by 5-aza-2'-deoxycytidine. | lld:pubmed |
| pubmed-article:11259619 | pubmed:affiliation | Division of Molecular Pharmacology, Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah 84112, USA. | lld:pubmed |
| pubmed-article:11259619 | pubmed:publicationType | Journal Article | lld:pubmed |
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