Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
Identifikátory výsledku
Kód výsledku v IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216224%3A14330%2F10%3A00044247" target="_blank" >RIV/00216224:14330/10:00044247 - isvavai.cz</a>
Výsledek na webu
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DOI - Digital Object Identifier
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Alternativní jazyky
Jazyk výsledku
angličtina
Název v původním jazyce
Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
Popis výsledku v původním jazyce
Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by the BCR-ABL oncogene. The BCR-ABL oncogene encodes constitutively active tyrosin kinase. It was previously shown, that transient inhibition of BCR-ABL bydasatinib is sufficient to commit CML cells to apoptosis (Shah 2008). Dasatinib mediated apoptosis in K562 cell line is accompanied by increasing expression level of proapoptotic protein BIM. Our results confirmed high mRNA levels of BIM in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM) dasatinib treatment. Intracellular level of BIM protein is regulated via phosphorylation by ERK protein kinase and subsequent degradation in the proteasome. In our research, we inhibited proteasome degradation by bortezomib. Combination of dasatinib and bortezomib led to rapid increase in BIM expression after 20 minutes.
Název v anglickém jazyce
Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
Popis výsledku anglicky
Chronic myeloid leukaemia (CML) is a clonal disorder of haematopoietic stem cells, characterized by the BCR-ABL oncogene. The BCR-ABL oncogene encodes constitutively active tyrosin kinase. It was previously shown, that transient inhibition of BCR-ABL bydasatinib is sufficient to commit CML cells to apoptosis (Shah 2008). Dasatinib mediated apoptosis in K562 cell line is accompanied by increasing expression level of proapoptotic protein BIM. Our results confirmed high mRNA levels of BIM in both transiently and continuously treated (100nM dasatinib) K562 cells compared to low dose continuous (1nM) dasatinib treatment. Intracellular level of BIM protein is regulated via phosphorylation by ERK protein kinase and subsequent degradation in the proteasome. In our research, we inhibited proteasome degradation by bortezomib. Combination of dasatinib and bortezomib led to rapid increase in BIM expression after 20 minutes.
Klasifikace
Druh
O - Ostatní výsledky
CEP obor
FD - Onkologie a hematologie
OECD FORD obor
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Návaznosti výsledku
Projekt
<a href="/cs/project/2B06052" target="_blank" >2B06052: Vytipování markerů, screening a časná diagnostika nádorových onemocnění pomocí vysoce automatizovaného zpracování multidimenzionálních biomedicínských obrazů</a><br>
Návaznosti
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Ostatní
Rok uplatnění
2010
Kód důvěrnosti údajů
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů