期刊
JOURNAL OF PROTEOME RESEARCH
卷 10, 期 2, 页码 404-415出版社
AMER CHEMICAL SOC
DOI: 10.1021/pr100468w
关键词
cancer; anti-cancer drugs; drug resistance; CEM T-Iymphoblastic leukemia; CDK inhibitor; proteomics; Rho GDP-dissociation inhibitor 2; Y-box binding protein 1; Hsp70/90 organizing protein; biomarker
资金
- Czech Ministry of School and Education [LC07017]
- Grant Agency of the Czech Republic GACR [301/08/1649]
- Operational Program Research and Development for Innovations [CZ.1.05/2.1.00/01.0030]
- Institutional Research Concepts [AV0Z50450515, AV0Z50200510]
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-Iymphoblastic 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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