The effect of proteasome inhibition on p53 degradation and proliferation in tonsil epithelial cells. Arch Otolaryngol Head Neck Surg 2008 Feb;134(2):157-63
Date
02/20/2008Pubmed ID
18283158DOI
10.1001/archoto.2007.37Scopus ID
2-s2.0-39649090495 (requires institutional sign-in at Scopus site) 6 CitationsAbstract
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.
Author List
Harris GF 4th, Anderson ME, Lee JHAuthor
Gerald F. Harris Emeritus Professor in the Orthopaedic Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsApoptosis
Caspase 3
Cell Proliferation
Cell Transformation, Neoplastic
Cells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells
Head and Neck Neoplasms
Humans
Leupeptins
Mice
Mice, Inbred C57BL
Mice, Knockout
Oncogene Proteins, Viral
Palatine Tonsil
Protease Inhibitors
Proteasome Inhibitors
Repressor Proteins
Tumor Suppressor Protein p53
