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Statements

Subject Item
n2:RIV%2F68378050%3A_____%2F13%3A00398204%21RIV14-AV0-68378050
rdf:type
n14:Vysledek skos:Concept
dcterms:description
Disruption of apoptotic pathways belongs to commonly reported molecular mechanisms that underlie cancer drug resistance. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, Apo2L) is a cytokine of the TNF family with selective anti-tumor activity and minimal toxicity toward healthy tissues. Primary leukemia cells are, however, largely intrinsically resistant to TRAIL-induced apoptosis. In this study we analyzed molecular differences between TRAIL-resistant K562 cell line and TRAIL-sensitive K562 clones. We demonstrate that TRAIL-sensitive K562 cells differ from the TRAIL-resistant cell line by cell surface downregulation of TRAIL decoy receptor 1, upregulation of both TRAIL death receptors, enhanced assembly and improved functioning of the death-inducing signaling complex, and increased cytoplasmic protein expression of CASP8 and key proapoptotic BCL2 members BID, BIM, BAD and BAK. The molecular basis of the intrinsic leukemia cell TRAIL resistance thus appears a consequence of the multi-level disruption of the extrinsic apoptotic pathway. The results of this study also suggest that the leukemia TRAIL-resistance is functional, leaving a possibility of overcoming the resistance by preexposure of the leukemia cells to potent TRAIL sensitizers, e.g. BH3-mimetics. Disruption of apoptotic pathways belongs to commonly reported molecular mechanisms that underlie cancer drug resistance. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL, Apo2L) is a cytokine of the TNF family with selective anti-tumor activity and minimal toxicity toward healthy tissues. Primary leukemia cells are, however, largely intrinsically resistant to TRAIL-induced apoptosis. In this study we analyzed molecular differences between TRAIL-resistant K562 cell line and TRAIL-sensitive K562 clones. We demonstrate that TRAIL-sensitive K562 cells differ from the TRAIL-resistant cell line by cell surface downregulation of TRAIL decoy receptor 1, upregulation of both TRAIL death receptors, enhanced assembly and improved functioning of the death-inducing signaling complex, and increased cytoplasmic protein expression of CASP8 and key proapoptotic BCL2 members BID, BIM, BAD and BAK. The molecular basis of the intrinsic leukemia cell TRAIL resistance thus appears a consequence of the multi-level disruption of the extrinsic apoptotic pathway. The results of this study also suggest that the leukemia TRAIL-resistance is functional, leaving a possibility of overcoming the resistance by preexposure of the leukemia cells to potent TRAIL sensitizers, e.g. BH3-mimetics.
dcterms:title
Multi-level disruption of the extrinsic apoptotic pathway mediates resistance of leukemia cells to TNF-related apoptosis-inducing ligand (TRAIL) Multi-level disruption of the extrinsic apoptotic pathway mediates resistance of leukemia cells to TNF-related apoptosis-inducing ligand (TRAIL)
skos:prefLabel
Multi-level disruption of the extrinsic apoptotic pathway mediates resistance of leukemia cells to TNF-related apoptosis-inducing ligand (TRAIL) Multi-level disruption of the extrinsic apoptotic pathway mediates resistance of leukemia cells to TNF-related apoptosis-inducing ligand (TRAIL)
skos:notation
RIV/68378050:_____/13:00398204!RIV14-AV0-68378050
n14:predkladatel
n15:ico%3A68378050
n3:aktivita
n11:I n11:S n11:V
n3:aktivity
I, S, V
n3:cisloPeriodika
2
n3:dodaniDat
n17:2014
n3:domaciTvurceVysledku
n4:9022643 n4:1713264
n3:druhVysledku
n9:J
n3:duvernostUdaju
n16:S
n3:entitaPredkladatele
n7:predkladatel
n3:idSjednocenehoVysledku
90081
n3:idVysledku
RIV/68378050:_____/13:00398204
n3:jazykVysledku
n10:eng
n3:klicovaSlova
leukemia; drug-resistance; TRAIL; apoptosis; BCL2 family
n3:klicoveSlovo
n5:drug-resistance n5:apoptosis n5:leukemia n5:TRAIL n5:BCL2%20family
n3:kodStatuVydavatele
SK - Slovenská republika
n3:kontrolniKodProRIV
[4CA9F6510B33]
n3:nazevZdroje
Neoplasma
n3:obor
n12:EB
n3:pocetDomacichTvurcuVysledku
2
n3:pocetTvurcuVysledku
12
n3:rokUplatneniVysledku
n17:2013
n3:svazekPeriodika
60
n3:tvurceVysledku
Molinsky, J. Leahomschi, S. Anděra, Ladislav Gasova, Z. Simonova, T. Nečas, E. Klener, P. Klener, P. jr. Trněný, M. Živný, J. Peterka, Martin Klánová, M.
n3:wos
000320086800015
s:issn
0028-2685
s:numberOfPages
9