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
Rok vydání: 2010
Předmět:
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