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.
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.
Institute of Animal Physiology and Genetics AS CR, vvi, Libechov, Czech Republic.
Helena
H
Skalnikova
Jirina
J
Martinkova
Rita
R
Hrabakova
Petr
P
Halada
Marta
M
Dziechciarkova
Marian
M
Hajduch
Suresh Jivan
SJ
Gadher
Andreas
A
Hammar
Daniel
D
Enetoft
Andreas
A
Ekefjard
Ola
O
Forsstrom-Olsson
Hana
H
Kovarova
D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D002851:Chromatography, High Pressure Liquid; D019295:Computational Biology; D004268:DNA-Binding Proteins / Q000378:metabolism*; D019008:Drug Resistance, Neoplasm; D020730:Guanine Nucleotide Dissociation Inhibitors / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D006801:Humans; D015151:Immunoblotting; D008954:Models, Biological; D009687:Nuclear Proteins / Q000378:metabolism*; D025941:Protein Interaction Mapping; D020543:Proteome / Q000032:analysis / Q000378:metabolism*; D011687:Purines / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013347:Subcellular Fractions / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000378:metabolism*; D051840:Y-Box-Binding Protein 1; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors
D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D020730:Guanine Nucleotide Dissociation Inhibitors; D006360:Heat-Shock Proteins; D009687:Nuclear Proteins; D020543:Proteome; D011687:Purines; C079373:STIP1 protein, human; D025521:Tumor Suppressor Proteins; D051840:Y-Box-Binding Protein 1; C070856:YBX1 protein, human; C118034:bohemine; D062947:rho-Specific Guanine Nucleotide Dissociation Inhibitors