The effect of proteasome inhibition on p53 degradation and proliferation in tonsil epithelial cells

George F. Harris IV, Mary E. Anderson, John H. Lee

Research output: Contribution to journalArticle

6 Scopus citations

Abstract

Objective: To determine whether proteasome inhibition could reverse E6-mediated p53 degradation, cause selective growth inhibition, and induce apoptosis in human papillomavirus E6-transformed primary tonsil epithelial cells. Design: Primary human and mouse tonsil epithelial cell lines were transformed with a retrovirus containing human papillomavirus 16 oncogenes. MG132 was used to inhibit proteasome degradation in vitro and in vivo, and biochemical assays regarding p53 and apoptosis were performed. Results: In cells that express E6, proteasome inhibition with MG132 restored p53 protein levels and decreased proliferation in a dose-dependent fashion that was significantly more pronounced compared with controls. However, inhibition of proliferation occurred at a lower concentration than restoration of p53 protein expression. Also, wild-type and p53 knockout mouse tonsil epithelial cells that express E6 had near-identical inhibition of growth, suggesting that growth inhibition was p53 independent. In vivo studies did not demonstrate any growth inhibition. Conclusion: The findings suggest that proteasome inhibition preferentially inhibits proliferation in cells expressing E6 through a p53-independent mechanism.

Original languageEnglish (US)
Pages (from-to)157-163
Number of pages7
JournalArchives of Otolaryngology - Head and Neck Surgery
Volume134
Issue number2
DOIs
StatePublished - Feb 1 2008

ASJC Scopus subject areas

  • Surgery
  • Otorhinolaryngology

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