Document Detail

Acetaldehyde activates Jun/AP-1 expression and DNA binding activity in human oral keratinocytes.
MedLine Citation:
PMID:  11978551     Owner:  NLM     Status:  MEDLINE    
Oral cancer is a significant health problem, particularly among individuals that ingest alcohol in combination with the use of tobacco products. The enhanced development of tobacco-initiated oral cancers by ethanol suggests that ethanol or one of its metabolites may act as a type of tumor promoter. Nevertheless, the mechanisms underlying the ability of ethanol to enhance oral carcinogenesis remain unclear. We hypothesize that acetaldehyde, the first metabolite of ethanol, may activate the expression and/or activity of Jun/AP-1 in oral keratinocytes analogous to the phorbol ester TPA and other tumor promoters in epidermal keratinocytes. To test this hypothesis, we treated HPV immortalized, non-tumorigenic human oral keratinocytes with acetaldehyde at various concentrations and for various times and measured several parameters of Jun/AP-1expression and function. Our results indicated that c-Jun mRNA and protein levels increased in the acetaldehyde treated cells compared to untreated control cells. Moreover, Jun/AP-1 DNA binding activity was rapidly activated by acetaldehyde in a dose-dependent fashion. The increases in Jun protein and AP-1 DNA binding activity were accompanied by increased transactivation of an AP-1 responsive reporter construct as well as increased transcript levels of a candidate AP-1 responsive gene, stromelysin 3. The levels of acetaldehyde employed were minimally toxic to the cells as determined by MTT assays. Thus, acetaldehyde was found to activate the expression and activity of an oncogenic transcription factor in HPV-initiated cells. Taken together, these results suggest that acetaldehyde may participate, at least in part, in the promotion stage of oral carcinogenesis.
Sherry R Timmons; Joseph O Nwankwo; Frederick E Domann
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Oral oncology     Volume:  38     ISSN:  1368-8375     ISO Abbreviation:  Oral Oncol.     Publication Date:  2002 Apr 
Date Detail:
Created Date:  2002-04-29     Completed Date:  2002-06-03     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  9709118     Medline TA:  Oral Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  281-90     Citation Subset:  IM    
Oral Sciences Graduate Program, B180ML, The University of Iowa, Iowa City, IA 52242, USA.
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MeSH Terms
Acetaldehyde / adverse effects*
Blotting, Western
Cell Line, Transformed
DNA / metabolism*
Dose-Response Relationship, Drug
Electrophoretic Mobility Shift Assay
Gene Expression
Keratinocytes / drug effects*,  metabolism
Matrix Metalloproteinase 11
Metalloendopeptidases / genetics
Protein Binding
Proto-Oncogene Proteins c-jun / drug effects*,  metabolism
RNA, Messenger / analysis
Transcription Factor AP-1 / drug effects*,  metabolism
Grant Support
Reg. No./Substance:
0/Proto-Oncogene Proteins c-jun; 0/RNA, Messenger; 0/Transcription Factor AP-1; 75-07-0/Acetaldehyde; 9007-49-2/DNA; EC 3.4.24.-/Matrix Metalloproteinase 11; EC 3.4.24.-/Metalloendopeptidases

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