Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2003-12-5
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
133-6
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Expression of the IAPs in multidrug resistant tumor cells.
pubmed:affiliation
Dipartimento di Scienze Farmacologiche, Università di Palermo, Via del Vespro 129, I-90127 Palermo, Italy.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't