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

Vito Spataro1, Katia Simmen, Claudio A Realini

  • 1Oncology Institute of Southern Switzerland, Ospedale La Carita, 6600 Locarno, TI, Switzerland.

Anticancer Research
|January 30, 2003
PubMed
Abstract

Insights

Overexpressing the proteasome subunit Rpn11 in mammalian cells increases resistance to chemotherapy drugs like vinblastine and cisplatin. This Rpn11 overexpression also slows cell proliferation, potentially aiding tumor cell survival.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Cell Biology

Background:

  • Identifying multidrug resistance (MDR) factors is critical for effective cancer chemotherapy.
  • Proteasome subunit dysfunction is implicated in cancer development and drug resistance.

Purpose of the Study:

  • To investigate the role of the proteasome subunit Rpn11 in multidrug resistance.
  • To analyze the impact of Rpn11 overexpression on cancer cell response to cytotoxic drugs.

Main Methods:

  • Analyzed Rpn11 expression levels in various cancer cell lines.
  • Utilized clonogenic cytotoxicity assays to assess drug resistance in cells overexpressing Rpn11.

Main Results:

  • Rpn11 expression varies significantly across different cancer cell types.
  • Stable Rpn11 overexpression conferred moderate resistance to vinblastine, cisplatin, and doxorubicin.
  • Cells overexpressing Rpn11 exhibited a reduced proliferation rate compared to control cells.

Conclusions:

  • Rpn11 overexpression influences mammalian cell proliferation and drug response.
  • These effects may contribute to tumor cell evasion of chemotherapy.
  • Rpn11 could serve as a potential biomarker for multidrug-resistant cancer cells.

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