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 14-3-3zeta mRNA in oral squamous cell carcinoma (OSCC) by differential display.


METHODS
The clinical relevance of 14-3-3zeta 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 NFkappaB, beta-catenin and Bcl-2.


RESULTS
Intense immunostaining of 14-3-3zeta protein was observed in 61/89 (69%) OPLs and 95/120 (79%) OSCCs. Immunohistochemistry showed significant increase in expression of 14-3-3zeta protein from normal mucosa to OPLs to OSCCs (ptrend < 0.001). Significant increase in expression of 14-3-3zeta 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 14-3-3zeta protein binds to NFkappaB, beta-catenin and Bcl-2, suggesting its involvement in cellular signaling, leading to proliferation of oral cancer cells.


CONCLUSIONS
Our findings suggest that over-expression of 14-3-3zeta is an early event in oral tumorigenesis and may have an important role in its development and progression. Thus, 14-3-3zeta may serve as an important molecular target for designing novel therapy for oral cancer.
Matta
Ajay
A
Department of Biochemistry, All India Institute of Medical Sciences, Ansari Nagar, New Delhi -110029, India. matta_ajay@rediffmail.com
Bahadur
Sudhir
S
Duggal
Ritu
R
Gupta
Siddhartha D
SD
Ralhan
Ranju
R
D048948:14-3-3 Proteins / Q000096:biosynthesis / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics*; D049109:Cell Proliferation; D015870:Gene Expression; D006801:Humans; D009062:Mouth Neoplasms / Q000235:genetics*
D048948:14-3-3 Proteins