Document Detail


The effect of proteasome inhibition on p53 degradation and proliferation in tonsil epithelial cells.
MedLine Citation:
PMID:  18283158     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
George F Harris; Mary E Anderson; John H Lee
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  Archives of otolaryngology--head & neck surgery     Volume:  134     ISSN:  0886-4470     ISO Abbreviation:  Arch. Otolaryngol. Head Neck Surg.     Publication Date:  2008 Feb 
Date Detail:
Created Date:  2008-02-19     Completed Date:  2008-05-08     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  8603209     Medline TA:  Arch Otolaryngol Head Neck Surg     Country:  United States    
Other Details:
Languages:  eng     Pagination:  157-63     Citation Subset:  AIM; IM    
Affiliation:
Department of Otolaryngology-Head and Neck Surgery, The University of Iowa, 200 Hawkins Dr, Iowa City, IA 52242-1078, USA.
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MeSH Terms
Descriptor/Qualifier:
Animals
Apoptosis / drug effects
Caspase 3 / metabolism
Cell Proliferation / drug effects
Cell Transformation, Neoplastic
Cells, Cultured
Dose-Response Relationship, Drug
Epithelial Cells / drug effects,  pathology*
Head and Neck Neoplasms / virology*
Humans
Leupeptins / pharmacology
Mice
Mice, Inbred C57BL
Mice, Knockout
Oncogene Proteins, Viral / metabolism*
Palatine Tonsil / cytology*,  virology
Protease Inhibitors / pharmacology*
Proteasome Endopeptidase Complex / antagonists & inhibitors
Repressor Proteins / metabolism*
Tumor Suppressor Protein p53 / metabolism*
Grant Support
ID/Acronym/Agency:
1-K08-DC0005627-1/DC/NIDCD NIH HHS; 5-T32-DC000040/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/E6 protein, Human papillomavirus type 16; 0/Leupeptins; 0/Oncogene Proteins, Viral; 0/Protease Inhibitors; 0/Repressor Proteins; 0/Tumor Suppressor Protein p53; 133407-82-6/benzyloxycarbonylleucyl-leucyl-leucine aldehyde; EC 3.4.22.-/Caspase 3; EC 3.4.25.1/Proteasome Endopeptidase Complex

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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