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Over-expression of 14-3-3zeta is an early event in oral cancer

BACKGROUND: The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. METHODS: The clinical relevance of 14-3-3ζ protein i...

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Autores principales: Matta, Ajay, Bahadur, Sudhir, Duggal, Ritu, Gupta, Siddhartha D, Ralhan, Ranju
Formato: Texto
Lenguaje:English
Publicado: BioMed Central 2007
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082039/
https://www.ncbi.nlm.nih.gov/pubmed/17764575
http://dx.doi.org/10.1186/1471-2407-7-169
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author Matta, Ajay
Bahadur, Sudhir
Duggal, Ritu
Gupta, Siddhartha D
Ralhan, Ranju
author_facet Matta, Ajay
Bahadur, Sudhir
Duggal, Ritu
Gupta, Siddhartha D
Ralhan, Ranju
author_sort Matta, Ajay
collection PubMed
description BACKGROUND: The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. METHODS: The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. RESULTS: Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (p(trend )< 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. CONCLUSION: Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer.
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spelling pubmed-20820392007-11-20 Over-expression of 14-3-3zeta is an early event in oral cancer Matta, Ajay Bahadur, Sudhir Duggal, Ritu Gupta, Siddhartha D Ralhan, Ranju BMC Cancer Research Article BACKGROUND: The functional and clinical significance of 14-3-3 proteins in human cancers remain largely undetermined. Earlier, we have reported differential expression of 14-3-3ζ mRNA in oral squamous cell carcinoma (OSCC) by differential display. METHODS: The clinical relevance of 14-3-3ζ protein in oral tumorigenesis was determined by immunohistochemistry in paraffin embedded sections of oral pre-malignant lesions (OPLs), OSCCs and histologically normal oral tissues and corroborated by Western Blotting. Co-immunoprecipitation assays were carried out to determine its association with NFκB, β-catenin and Bcl-2. RESULTS: Intense immunostaining of 14-3-3ζ protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3ζ protein from normal mucosa to OPLs to OSCCs (p(trend )< 0.001). Significant increase in expression of 14-3-3ζ protein was observed as early as in hyperplasia (p = 0.009), with further elevation in moderate and severe dysplasia, that was sustained in OSCCs. These findings were validated by Western blotting. Using Co-immunoprecipitation, we demonstrated that 14-3-3ζ protein binds to NFκB, β-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells. CONCLUSION: Our findings suggest that over-expression of 14-3-3ζ is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3ζ may serve as an important molecular target for designing novel therapy for oral cancer. BioMed Central 2007-09-02 /pmc/articles/PMC2082039/ /pubmed/17764575 http://dx.doi.org/10.1186/1471-2407-7-169 Text en Copyright © 2007 Matta et al; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( (http://creativecommons.org/licenses/by/2.0) ), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Matta, Ajay
Bahadur, Sudhir
Duggal, Ritu
Gupta, Siddhartha D
Ralhan, Ranju
Over-expression of 14-3-3zeta is an early event in oral cancer
title Over-expression of 14-3-3zeta is an early event in oral cancer
title_full Over-expression of 14-3-3zeta is an early event in oral cancer
title_fullStr Over-expression of 14-3-3zeta is an early event in oral cancer
title_full_unstemmed Over-expression of 14-3-3zeta is an early event in oral cancer
title_short Over-expression of 14-3-3zeta is an early event in oral cancer
title_sort over-expression of 14-3-3zeta is an early event in oral cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2082039/
https://www.ncbi.nlm.nih.gov/pubmed/17764575
http://dx.doi.org/10.1186/1471-2407-7-169
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