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.

Institute of Animal Physiology and Genetics AS CR, vvi, Libechov, Czech Republic.

Journal of proteome research 2011 Feb 4

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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.

Citation

Helena Skalnikova, Jirina Martinkova, Rita Hrabakova, Petr Halada, Marta Dziechciarkova, Marian Hajduch, Suresh Jivan Gadher, Andreas Hammar, Daniel Enetoft, Andreas Ekefjard, Ola Forsstrom-Olsson, Hana Kovarova. 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. Journal of proteome research. 2011 Feb 4;10(2):404-15