The essential 26S proteasome subunit Rpn11 confers multidrug resistance to mammalian cells.

Background: 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. Materials and Methods: We analyzed the expression levels of the proteasome subunit Rpnll in a panel of cancer cell lines, and studied the effect of Rpnll overexpression on the resistance of mammalian cells to cytotoxic drugs in clonogenic cytotoxicity assay. Results: Rpnll levels are highly variable in cancer cells; mammalian cells stably overexpressing Rpnll display moderate resistance to vinblastine, cisplatin and doxorubicin, and also exhibit a slower proliferation rate when compared to the control cells. Conclusion: Rpnll-overexpression in mammalian cells affects cell proliferation and the response to cytotoxic drags, both of which may promote tumor cell escape from chemotherapeutic agents, and may serve as a marker for MDR-cells.