Source:http://linkedlifedata.com/resource/pubmed/id/14654915
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
1
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pubmed:dateCreated |
2003-12-5
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pubmed:abstractText |
We have investigated the expression of the IAPs (inhibitory of apoptosis proteins) in the human HL-60 leukemia and in its multidrug resistant, P-glycoprotein (P-gp) over-expressing variant, HL-60R. HL-60R exhibits resistance to apoptosis induced from P-gp substrate drugs and also from other triggers (cisplatin, TNF-alpha, Fas ligation, TRAIL, IFN-gamma and serum starvation) not related to the multidrug transporter. Except for c-IAP-1 mRNA, HL-60R significantly over-expressed both the mRNAs and the proteins of all the IAPs studied, i.e. c-IAP-1, c-IAP-2, XIAP, NAIP and survivin. Determination of the DNA-binding capacity of NF-kappaB (p50 or p65 subunits) indicated that, while HL-60 cells show constitutive activation of p50 only, HL-60R cells contain the activated forms of both p50 and p65. Since p65 is necessary to form the NF-kappaB heterodimers able to increase transcription, its presence in HL-60R cells might well correlate to their increased levels of IAPs and, possibly of P-gp, which, reportedly, are NF-kappaB target genes. These results underline the possible role that the coordinated over-expression of the different IAPs may play in tumor cell resistance to drug induced apoptosis. Inhibition of NF-kappaB might be a useful strategy to block their up-regulation.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1021-335X
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
11
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
133-6
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:14654915-Apoptosis,
pubmed-meshheading:14654915-Blotting, Western,
pubmed-meshheading:14654915-Drug Resistance, Multiple,
pubmed-meshheading:14654915-Drug Resistance, Neoplasm,
pubmed-meshheading:14654915-Gene Expression Regulation, Neoplastic,
pubmed-meshheading:14654915-HL-60 Cells,
pubmed-meshheading:14654915-Humans,
pubmed-meshheading:14654915-Inhibitor of Apoptosis Proteins,
pubmed-meshheading:14654915-Proteins,
pubmed-meshheading:14654915-RNA, Messenger,
pubmed-meshheading:14654915-Reverse Transcriptase Polymerase Chain Reaction
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pubmed:year |
2004
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pubmed:articleTitle |
Expression of the IAPs in multidrug resistant tumor cells.
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pubmed:affiliation |
Dipartimento di Scienze Farmacologiche, Università di Palermo, Via del Vespro 129, I-90127 Palermo, Italy.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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