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Epidermal growth factor receptor vIII expression in U87 glioblastoma cells alters their proteasome composition,

Kwanghee Kim1, James M Brush, Philip A Watson

  • 1Department of Radiation Oncology, David Geffen School of Medicine at University of California at Los Angeles, Los Angeles, CA 90095-1714, USA.

Molecular Cancer Research : MCR
|March 14, 2008
PubMed

Insights

The epidermal growth factor receptor vIII (EGFRvIII) mutant alters proteasome composition and function in glioblastoma cells, impacting their response to irradiation. This EGFRvIII-induced change affects proteasome subunit expression and radioresistance.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Molecular Biology

Background:

  • The 26S proteasome regulates protein degradation, crucial for cellular function and a target in cancer therapy.
  • Irradiation typically inhibits proteasome activity in most cell types.
  • U87 glioblastoma cells expressing epidermal growth factor receptor vIII (EGFRvIII) present an exception to irradiation-induced proteasome inhibition.

Purpose of the Study:

  • To investigate the factors influencing proteasome structure and activity in cancer cells.
  • To understand why U87EGFRvIII cells resist irradiation-induced proteasome inhibition.
  • To determine if EGFRvIII expression alters proteasome composition and function.

Main Methods:

  • Quantitative reverse transcription-PCR to measure proteasome subunit expression (constitutive, inducible, 11S, 19S components).
  • Assessing proteasome activity using fluorogenic substrates and a reporter gene (cODCZsGreen).
  • Comparing proteasome subunit expression and c-myc levels in U87 and U87EGFRvIII cells after irradiation or proteasome inhibitor treatment.

Main Results:

  • U87EGFRvIII cells showed no significant inhibition of 26S proteasome activity upon irradiation, unlike standard U87 cells.
  • Significant differences in proteasome subunit and immunosubunit expression were observed between U87 and U87EGFRvIII cells.
  • Irradiation of U87 cells increased proteasome subunit expression and decreased c-myc levels, effects largely absent in U87EGFRvIII cells.

Conclusions:

  • Expression of the EGFRvIII mutant significantly alters the composition and function of the 26S proteasome in glioblastoma cells.
  • These proteasome alterations in U87EGFRvIII cells may contribute to their observed radioresistance.
  • Further research is needed to establish the precise relationship between EGFRvIII-mediated proteasome changes and radioresistance.

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