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
Language English Country United States Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
21067243
DOI
10.1021/pr100468w
Knihovny.cz E-resources
- MeSH
- Models, Biological MeSH
- Drug Resistance, Neoplasm * MeSH
- DNA-Binding Proteins metabolism MeSH
- Immunoblotting MeSH
- Guanine Nucleotide Dissociation Inhibitors metabolism MeSH
- Nuclear Proteins metabolism MeSH
- Humans MeSH
- Protein Interaction Mapping MeSH
- Cell Line, Tumor MeSH
- Tumor Suppressor Proteins metabolism MeSH
- Y-Box-Binding Protein 1 MeSH
- Heat-Shock Proteins metabolism MeSH
- Proteome analysis metabolism MeSH
- Antineoplastic Agents pharmacology MeSH
- Purines pharmacology MeSH
- rho-Specific Guanine Nucleotide Dissociation Inhibitors MeSH
- Spectrophotometry, Ultraviolet MeSH
- Subcellular Fractions metabolism MeSH
- Computational Biology MeSH
- Chromatography, High Pressure Liquid MeSH
- Check Tag
- Humans MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- bohemine MeSH Browser
- DNA-Binding Proteins MeSH
- Guanine Nucleotide Dissociation Inhibitors MeSH
- Nuclear Proteins MeSH
- Tumor Suppressor Proteins MeSH
- Y-Box-Binding Protein 1 MeSH
- Heat-Shock Proteins MeSH
- Proteome MeSH
- Antineoplastic Agents MeSH
- Purines MeSH
- rho-Specific Guanine Nucleotide Dissociation Inhibitors MeSH
- STIP1 protein, human MeSH Browser
- YBX1 protein, human MeSH Browser
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.
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