Document Detail


Gaining insights into the Bcr-Abl activity-independent mechanisms of resistance to imatinib mesylate in KCL22 cells: a comparative proteomic approach.
MedLine Citation:
PMID:  20417730     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Imatinib mesylate is a potent inhibitor of Bcr-Abl tyrosine kinase, an oncoprotein that plays a key role in the development of chronic myeloid leukemia. Consequently, imatinib is used as front-line therapy for this disease. A major concern in imatinib treatment is the emergence of resistance to the drug. Here we used the imatinib-resistant KCL22R and imatinib-sensitive KCL22S cells in which none of the known resistance mechanisms has been detected and hence novel Bcr-Abl activity-independent mechanisms could be envisaged. We characterized proteins that were differentially expressed between the KCL22R and KCL22S cells. Using two-dimensional differential gel electrophoresis coupled with mass spectrometry and Western blot analysis we identified 51 differentially expressed proteins: 27 were over-expressed and 24 were under-expressed in KCL22R versus KCL22S cells. Several of these proteins are likely to be involved in such survival mechanisms as modulation of redox balance and activation of anti-apoptotic pathways mediated by NF-kappaB and Ras-MAPK signaling. The data reported may be useful for further studies on mechanisms of imatinib resistance and for the screening of biomarkers to develop new combinatorial therapeutic approaches.
Authors:
Irene Colavita; Nicola Esposito; Rosanna Martinelli; Francesca Catanzano; Junia V Melo; Fabrizio Pane; Margherita Ruoppolo; Francesco Salvatore
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-04-24
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1804     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-08-30     Completed Date:  2010-11-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1974-87     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. All rights reserved.
Affiliation:
CEINGE Biotecnologie Avanzate Scarl, Napoli, Italy.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / therapeutic use*
Blotting, Western
Drug Resistance, Neoplasm*
Electrophoresis, Gel, Two-Dimensional
Fusion Proteins, bcr-abl / genetics,  metabolism*
Glutathione / metabolism
Humans
Leukemia, Myelogenous, Chronic, BCR-ABL Positive / drug therapy*,  pathology
NADP / metabolism
Piperazines / therapeutic use*
Proteome / analysis*
Pyrimidines / therapeutic use*
RNA, Messenger / genetics
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Tumor Cells, Cultured
Tumor Markers, Biological / metabolism*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Fusion Proteins, bcr-abl; 0/Piperazines; 0/Proteome; 0/Pyrimidines; 0/RNA, Messenger; 0/Tumor Markers, Biological; 152459-95-5/imatinib; 53-59-8/NADP; 70-18-8/Glutathione

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


Previous Document:  Effects of Hyperoxia on the Dynamics of Skeletal Muscle Oxygenation at the Onset of Heavy-Intensity ...
Next Document:  Structural basis for the different activities of yeast Grx1 and Grx2.