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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Adenosine Triphosphatases, Animals, Antineoplastic Agents, COS Cells, Cell Line, Transformed, Cell Survival, Cisplatin, Doxorubicin, Drug Resistance, Multiple, Endopeptidases, Female, Hemagglutinins, Humans, Melphalan, Ovarian Neoplasms, Proteasome Endopeptidase Complex, Recombinant Fusion Proteins, Tumor Cells, Cultured, Vinblastine.
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Does the essential 26S proteasome subunit Rpn11 confer multidrug resistance to mammalian cells? Context: Identification of multidrug resistance (MDR) factors is crucial for designing chemotherapeutic strategies. Aberrant expression and dysfunction of proteasome subunits have been involved in malignant transformation and in cell resistance to various cytotoxic drugs. We analyzed the expression levels of the proteasome subunit Rpn11 in a panel of cancer cell lines, and studied the effect of Rpn11 overexpression on the resistance of mammalian cells to cytotoxic drugs in clonogenic cytotoxicity assay. Rpn11 levels are highly variable in cancer cells; mammalian cells stably overexpressing Rpn11 display moderate resistance to vinblastine, cisplatin and doxorubicin, and also exhibit a slower proliferation rate when compared to the control cells.
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Rpn11-overexpression in mammalian cells affects cell proliferation and the response to cytotoxic drugs, both of which may promote tumor cell escape from chemotherapeutic agents, and may serve as a marker for MDR-cells. Final Decision: yes