Cancer Drug-Resistance and a Look at Specific Proteins: Rho GDP-Dissociation Inhibitor 2, Y-Box Binding Protein 1, and HSP70/90 Organizing Protein in Proteomics Clinical Application
Autor: | Jirina Martinkova, Marian Hajduch, Daniel Enetoft, Ola Forsstrom-Olsson, Hana Kovarova, Suresh Jivan Gadher, Helena Kupcova Skalnikova, Marta Dziechciarkova, Andreas Hammar, Andreas Ekefjard, Rita Hrabakova, Petr Halada |
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Rok vydání: | 2010 |
Předmět: |
Proteome
Immunoblotting Cell Antineoplastic Agents Drug resistance Biology Proteomics Models Biological Biochemistry Cell Line Tumor Protein Interaction Mapping medicine Humans rho-Specific Guanine Nucleotide Dissociation Inhibitors Chromatography High Pressure Liquid Heat-Shock Proteins Guanine Nucleotide Dissociation Inhibitors Kinase Tumor Suppressor Proteins Binding protein Computational Biology Nuclear Proteins General Chemistry Y box binding protein 1 Cell biology DNA-Binding Proteins medicine.anatomical_structure Drug Resistance Neoplasm Purines Spectrophotometry Ultraviolet Y-Box-Binding Protein 1 CDK inhibitor Subcellular Fractions |
Zdroj: | Journal of Proteome Research. 10:404-415 |
ISSN: | 1535-3907 1535-3893 |
DOI: | 10.1021/pr100468w |
Popis: | Resistance to anti-cancer drugs is a well recognized problem and very often it is responsible for failure of the cancer treatment. In this study, the proteome alterations associated with the development of acquired resistance to cyclin-depedent kinases inhibitor bohemine, a promising anti-cancer drug, were analyzed with the primary aim of identifying potential targets of resistance within the cell that could pave a way to selective elimination of specific resistant cell types. A model of parental susceptible CEM T-lymphoblastic leukemia cells and its resistant counterpart CEM-BOH was used and advanced 2-D liquid chromatography was applied to fractionate cellular proteins. Differentially expressed identified proteins were further verified using immunoblotting and immunohistochemistry. Our study has revealed that Rho GDP-dissociation inhibitor 2, Y-box binding protein 1, and the HSP70/90 organizing protein have a critical role to play in resistance to cyclin-depedent kinases inhibitor. The results indicated not only that quantitative protein changes play an important role in drug-resistance, but also that there are various other parameters such as truncation, post-translational modification(s), and subcellular localization of selected proteins. Furthermore, these proteins were validated for their roles in drug resistance using different cell lines resistant to diverse representatives of anti-cancer drugs such as vincristine and daunorubicin. |
Databáze: | OpenAIRE |
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