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1.
J Proteome Res ; 10(2): 404-15, 2011 Feb 04.
Article in English | MEDLINE | ID: mdl-21067243

ABSTRACT

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.


Subject(s)
DNA-Binding Proteins/metabolism , Drug Resistance, Neoplasm , Guanine Nucleotide Dissociation Inhibitors/metabolism , Heat-Shock Proteins/metabolism , Nuclear Proteins/metabolism , Proteome/metabolism , Tumor Suppressor Proteins/metabolism , Antineoplastic Agents/pharmacology , Cell Line, Tumor , Chromatography, High Pressure Liquid , Computational Biology , Humans , Immunoblotting , Models, Biological , Protein Interaction Mapping , Proteome/analysis , Purines/pharmacology , Spectrophotometry, Ultraviolet , Subcellular Fractions/metabolism , Y-Box-Binding Protein 1 , rho-Specific Guanine Nucleotide Dissociation Inhibitors
3.
J Proteome Res ; 6(8): 3011-20, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17608511

ABSTRACT

In search for a strawberry (Fragaria ananassa) with low allergen content, we determined the proteomic variation within and between different varieties. Proteomics data were generated by DIGE and proteins identified with MALDI-MS/MS. The amount of the strawberry allergen Fra a 1 varied between different strawberry varieties (CV = 39%). The variation was at the same level, or even slightly larger, due to different growth conditions (CV = 43%). For 153 other proteins, the biological variation was more affected by different growth conditions than by different varieties (mean CV = 52% and 43%, respectively) due to variation in a subset of proteins. Thus, the allergen variation due to growth conditions must be taken into consideration in attempts to obtain a low-allergen strawberry. However, the allergen content was always lower in colorless (white) strawberry varieties than in the red ones. Moreover, of the spots whose expression correlated with the allergen and the color (32 and 68, respectively), only 3 were the same. This implies that these two phenotypic traits are not inseparable, and it may be possible to breed a red strawberry with low amount of allergen.


Subject(s)
Allergens/metabolism , Antigenic Variation/immunology , Antigens, Plant/metabolism , Fragaria/metabolism , Proteome/metabolism , Allergens/immunology , Antigens, Plant/immunology , Electrophoresis, Gel, Two-Dimensional , Proteome/immunology , Species Specificity
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