Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
The result's identifiers
Result code in 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>
Result on the web
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DOI - Digital Object Identifier
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Alternative languages
Result language
angličtina
Original language name
Dasatinib suppresses MEK/ERK pathway activity without sustained BCR-ABL inhibition and promotes BIM dependent apoptosis in chronic myeloid leukaemia cells.
Original language description
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.
Czech name
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Czech description
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Classification
Type
O - Miscellaneous
CEP classification
FD - Oncology and haematology
OECD FORD branch
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Result continuities
Project
<a href="/en/project/2B06052" target="_blank" >2B06052: Determination of markers, screening and early diagnostics of cancer diseases using highly automated processing of multidimensional biomedical images</a><br>
Continuities
P - Projekt vyzkumu a vyvoje financovany z verejnych zdroju (s odkazem do CEP)
Others
Publication year
2010
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů