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rdf:type |
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lifeskim:mentions |
umls-concept:C0007634,
umls-concept:C0025914,
umls-concept:C0026809,
umls-concept:C0032405,
umls-concept:C0033684,
umls-concept:C0041904,
umls-concept:C0087111,
umls-concept:C0162493,
umls-concept:C0205217,
umls-concept:C0242643,
umls-concept:C0376623,
umls-concept:C0596130,
umls-concept:C0683598,
umls-concept:C1704222
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pubmed:issue |
15
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pubmed:dateCreated |
2000-8-31
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pubmed:abstractText |
Mouse embryo fibroblasts lacking poly(ADP-ribose) polymerase (PARP)-1 express a barely detectable level of wild-type (wt) p53 protein. Doxorubicin at concentrations activating wt p53 in normal mouse embryo fibroblasts failed to induce it in mutant cells. wt p53 was only activated in response to a 10-fold higher doxorubicin dose. Treatment with higher doxorubicin concentrations was cytotoxic for normal but not for PARP-1 -/- cells. The latter was also resistant to other anticancer agents. The increased resistance of mutant cells to drugs resembled a unique phenomenon known as multidrug resistance (MDR). Interestingly, the MDR gene product P-glycoprotein was clearly up-regulated in PARP-1-deficient cells as compared with normal counterparts. Pretreatment with verapamil reversed the MDR phenotype.
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pubmed:commentsCorrections |
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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 |
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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 |
1
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pubmed:volume |
60
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
4238-44
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:10945636-Animals,
pubmed-meshheading:10945636-Antineoplastic Agents,
pubmed-meshheading:10945636-Breast Neoplasms,
pubmed-meshheading:10945636-Clone Cells,
pubmed-meshheading:10945636-Dose-Response Relationship, Drug,
pubmed-meshheading:10945636-Doxorubicin,
pubmed-meshheading:10945636-Drug Resistance, Multiple,
pubmed-meshheading:10945636-Drug Resistance, Neoplasm,
pubmed-meshheading:10945636-Embryo, Mammalian,
pubmed-meshheading:10945636-Fibroblasts,
pubmed-meshheading:10945636-Gene Expression Regulation,
pubmed-meshheading:10945636-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:10945636-Humans,
pubmed-meshheading:10945636-Mice,
pubmed-meshheading:10945636-Mice, Knockout,
pubmed-meshheading:10945636-P-Glycoprotein,
pubmed-meshheading:10945636-Poly(ADP-ribose) Polymerases,
pubmed-meshheading:10945636-Probenecid,
pubmed-meshheading:10945636-Tumor Cells, Cultured,
pubmed-meshheading:10945636-Tumor Suppressor Protein p53,
pubmed-meshheading:10945636-Up-Regulation,
pubmed-meshheading:10945636-Verapamil
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pubmed:year |
2000
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pubmed:articleTitle |
Increased resistance to anticancer therapy of mouse cells lacking the poly(ADP-ribose) polymerase attributable to up-regulation of the multidrug resistance gene product P-glycoprotein.
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pubmed:affiliation |
Institute of Cancer Research, University of Vienna, Austria.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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