Document Detail


Clinical significance of TC21 overexpression in oral cancer.
MedLine Citation:
PMID:  20040018     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In search of novel molecular markers for oral cancer, we reported increased levels of TC21/R-Ras2 transcripts in oral squamous cell carcinoma by differential display. The aim of this study was to determine the clinical significance of TC21 in oral cancer. METHODS: Immunohistochemical analysis of TC21 protein expression was carried out in 120 leukoplakias, 83 OSCCs and 30 non-malignant tissues, confirmed by immunoblotting, and correlated with clinicopathological parameters as well as disease prognosis. Co-immunoprecipitation assays were carried out to identify the interaction partners of TC21 protein in oral cancer cells and tissues. RESULTS: TC21 nuclear expression increased from normal oral tissues to leukoplakia and frank malignancy (P < 0.001). TC21 overexpression was observed in 74.2% leukoplakia with no dysplasia, 75.9% dysplasias and 79.5% OSCCs in comparison with normal oral tissues. Receiver operating characteristic analysis showed that the area-under-the curve values were 0.895, 0.885, and 0.919, while the positive predictive values were 95.8%, 95.6%, and 97.1%, for nuclear immunostaining for normal versus leukoplakia with no dysplasia, leukoplakic lesions with dysplasia, and OSCCs, respectively. Immunoblotting confirmed overexpression of TC21 in oral lesions. Using co-immunoprecipitation assays, we showed interactions of TC21 with Erk2, PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells. CONCLUSION: Our findings suggested that alteration in TC21 expression is an early event in oral cancer and correlates with poor prognosis of OSCCs. TC21 interactions with Erk2, PI3-K, 14-3-3zeta and 14-3-3sigma proteins in oral cancer cells and tissues suggests the involvement of TC21 in signaling pathways in oral cancer.
Authors:
Muzafar A Macha; Ajay Matta; Uma Sriram; Alok Thakkar; N K Shukla; Siddhartha Datta Gupta; Ranju Ralhan
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-12-16
Journal Detail:
Title:  Journal of oral pathology & medicine : official publication of the International Association of Oral Pathologists and the American Academy of Oral Pathology     Volume:  39     ISSN:  1600-0714     ISO Abbreviation:  J. Oral Pathol. Med.     Publication Date:  2010 Jul 
Date Detail:
Created Date:  2010-07-20     Completed Date:  2010-11-02     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8911934     Medline TA:  J Oral Pathol Med     Country:  Denmark    
Other Details:
Languages:  eng     Pagination:  477-85     Citation Subset:  D; IM    
Affiliation:
Department of Biochemistry, All India Institute of Medical Sciences, New Delhi, India.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 3-Kinase / metabolism
14-3-3 Proteins / metabolism
Adult
Aged
Carcinoma, Squamous Cell / genetics,  metabolism*,  pathology
Cell Line, Tumor
Cell Nucleus / metabolism
Disease-Free Survival
Exonucleases / metabolism
Gene Expression
Humans
Immunoprecipitation
Kaplan-Meiers Estimate
Leukoplakia, Oral / genetics,  metabolism*,  pathology
Membrane Proteins / biosynthesis*,  genetics
Middle Aged
Mitogen-Activated Protein Kinase 1 / metabolism
Monomeric GTP-Binding Proteins / biosynthesis*,  genetics
Mouth Neoplasms / genetics,  metabolism*,  pathology
Prognosis
ROC Curve
Signal Transduction
Tumor Markers, Biological / biosynthesis*,  genetics,  metabolism
Up-Regulation
Chemical
Reg. No./Substance:
0/14-3-3 Proteins; 0/Membrane Proteins; 0/Tumor Markers, Biological; EC 2.7.1.137/1-Phosphatidylinositol 3-Kinase; EC 2.7.11.24/MAPK1 protein, human; EC 2.7.11.24/Mitogen-Activated Protein Kinase 1; EC 3.1.-/Exonucleases; EC 3.1.-/SFN protein, human; EC 3.6.1/RRAS2 protein, human; EC 3.6.5.2/Monomeric GTP-Binding Proteins

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


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