Document Detail

Transactivation and expression patterns of Jun and Fos/AP-1 super-family proteins in human oral cancer.
MedLine Citation:
PMID:  19653276     Owner:  NLM     Status:  MEDLINE    
Transcription factor activator protein-1 (AP-1) super-family is known to modulate expression of array of genes during development of many cancers and considered as an important target for modern therapeutics. But the role of AP-1 during development of human oral cancers is still poorly understood. Because oral cancer is one of the most common cancers in India and south-east Asia, we studied the activation and expression pattern of AP-1 family of proteins and mRNA in different stages of oral carcinogenesis. Gel-shift assay, western blotting, immunohistochemistry and northern blotting have been used to assess the binding activity and expression pattern of AP-1 family (c-Jun, JunB, JunD, c-Fos, FosB, Fra-1 and Fra-2) proteins and mRNA transcripts in a total of 100 fresh oral tissue specimens comprising precancer (n = 40), cancer (n = 50) and healthy control (n = 10). Constitutive activation of AP-1 with concomitant upregulated expression of majority of AP-1 family of proteins and mRNA was observed in cancer cases. Interestingly, almost all precancerous cases showed JunD homodimers, whereas c-Fos/JunD was the most prevalent complex found in cancer tissues. The overexpression of EGFR mRNA, p50:p50/NF-kappaB homodimer formation, together with overexpression of pERK and c-Fos proteins in this study suggests an interesting cross talk between AP-1 and NF-kappaB pathways in oral cancers. Thus, this study demonstrates differential expression and activation of AP-1 super-family proteins in relation to severity of lesion and their crucial role in human oral carcinogenesis.
Alok Mishra; Alok C Bharti; Daman Saluja; Bhudev C Das
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  126     ISSN:  1097-0215     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2010 Feb 
Date Detail:
Created Date:  2009-12-28     Completed Date:  2010-02-01     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  819-29     Citation Subset:  IM    
Laboratory of Molecular Biology, National Cancer Institute, NIH, Bethesda, MD 20892, USA.
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MeSH Terms
Blotting, Northern
Carcinoma, Squamous Cell / genetics,  metabolism,  pathology
Cell Cycle / genetics
DNA Primers
Disease Progression
Gene Expression Regulation, Neoplastic
Genes, fos*
Genes, jun*
Gingiva / pathology
Lip / pathology
Middle Aged
Mouth Neoplasms / genetics*,  metabolism,  pathology
NF-kappa B / genetics
Oncogene Proteins v-fos / genetics*
Receptor, Epidermal Growth Factor / genetics
Tongue / pathology
Transcription Factor AP-1 / genetics*,  metabolism
Transcription, Genetic
Transcriptional Activation*
Reg. No./Substance:
0/DNA Primers; 0/NF-kappa B; 0/Oncogene Proteins v-fos; 0/Transcription Factor AP-1; EC, Epidermal Growth Factor

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