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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2002-3-28
pubmed:abstractText
Defects in apoptosis have been implicated in chemoresistance of colon cancer cells. We report here the ability to resist to 5-fluorouracil-induced apoptosis of 8 colon cancer cell lines differing in p53 and bax status: p53(-/0)bax(+/+) for TC7, SW480, HT-29; p53(+/+)bax(-/-) for LS174T, LoVo; p53(+/+) bax(+/-) for HCT116; p53(+/+) or p53(+/0)bax(+/+) for LS513 or HCT-EB, respectively. To approximate to the in vivo therapy, the cell lines were exposed to a long-term treatment of 5-FU. The analysis of proteins implicated in the apoptotic pathway has shown that the independent analysis of p53 or bax status was not sufficient to predict the extent of drug-resistance of all cell lines. In p53(+/+) cell lines but not in p53(-/0) cell lines, a low level of the pro-apoptotic Bax protein was correlated with a greater resistance of cells to 5-FU. In addition, we found that high levels of anti-apoptotic Bcl-2 and Bcl-x(L) proteins combined with a low level of Bax were correlated to high 5-FU resistance of wild-type p53 cell lines. The same correlation was obtained for 2 out of 3 mutated p53 cell lines. In conclusion, the relative levels of Bcl-2, Bcl-x(L) and Bax may altogether contribute to determine the resistance of a majority of colon tumor cells to long-term 5-FU treatment, whatever their p53 status.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0020-7136
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
98
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
498-504
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:11920608-Antimetabolites, Antineoplastic, pubmed-meshheading:11920608-Blotting, Western, pubmed-meshheading:11920608-Colonic Neoplasms, pubmed-meshheading:11920608-Drug Resistance, Neoplasm, pubmed-meshheading:11920608-Fluorouracil, pubmed-meshheading:11920608-Genotype, pubmed-meshheading:11920608-HT29 Cells, pubmed-meshheading:11920608-Humans, pubmed-meshheading:11920608-Mutation, pubmed-meshheading:11920608-Phenotype, pubmed-meshheading:11920608-Proto-Oncogene Proteins, pubmed-meshheading:11920608-Proto-Oncogene Proteins c-bcl-2, pubmed-meshheading:11920608-Time Factors, pubmed-meshheading:11920608-Tumor Cells, Cultured, pubmed-meshheading:11920608-Tumor Suppressor Protein p53, pubmed-meshheading:11920608-bcl-2-Associated X Protein, pubmed-meshheading:11920608-bcl-X Protein
pubmed:year
2002
pubmed:articleTitle
Resistance of colon cancer cells to long-term 5-fluorouracil exposure is correlated to the relative level of Bcl-2 and Bcl-X(L) in addition to Bax and p53 status.
pubmed:affiliation
INSERM U505, Université Pierre et Marie Curie, Paris, France.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't