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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Spataro
Vito
V
Oncology Institute of Southern Switzerland, Ospedale La Carita, 6600 Locarno, TI, Switzerland.
Simmen
Katia
K
Realini
Claudio A
CA
D000251:Adenosine Triphosphatases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D019556:COS Cells / Q000187:drug effects / Q000502:physiology; D002461:Cell Line, Transformed; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D018432:Drug Resistance, Multiple / Q000502:physiology*; D010450:Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D005260:Female; D006388:Hemagglutinins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008558:Melphalan / Q000494:pharmacology; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014747:Vinblastine / Q000494:pharmacology
D000970:Antineoplastic Agents; D006388:Hemagglutinins; D011993:Recombinant Fusion Proteins; D014747:Vinblastine; D004317:Doxorubicin; D010450:Endopeptidases; D046988:Proteasome Endopeptidase Complex; C119011:26S proteasome non-ATPase regulatory subunit 13; D000251:Adenosine Triphosphatases; D002945:Cisplatin; D008558:Melphalan