Overexpression of AKT in Oral Squamous Cell Carcinoma

Aberration of signal transducers in PI3K/AKT pathway has been found in many human cancers and may play a role in carcinogenesis of those cancers. Objectives: The objectives of the present study were (1) to investigate protein expression of pan AKT and its phosphorylated form, p-AKT, in oral squamous cell carcinoma (OSCC) tissues of 20 Thai patients and (2) to analyze mRNA expression of three isoforms of AKT; AKT-1, -2, and -3 and protein expression of pan AKT in four OSCC cell lines and human oral keratinocytes (HOK). Methods: The expression of pan AKT and p-AKT in OSCC tissues was studied by immunohistochemistry. The mRNA expression of AKT-1, -2, and -3 in OSCC cell lines and HOK was analyzed by RT-PCR and the protein expression of pan AKT was studied by Western blot assay. Results: The results showed that pan AKT and p-AKT were overexpressed in 95% and 100% of OSCC cases, respectively. We observed more intense expression of pan AKT and p-AKT at the invasive fronts of some OSCC tissues. Pan AKT protein was also overexpressed in all OSCC cell lines in comparison with HOK. Interestingly, AKT-1 and -2 mRNA of OSCC cell lines were only constitutively expressed in comparison with HOK. AKT-3 mRNA appeared to be minimally expressed in OSCC cell lines and HOK. Conclusion: These findings suggested that overexpression of pan AKT and p-AKT may be involved with OSCC carcinogenesis and post-transcriptional modification of the expression of AKT isoforms in OSCC may occur. Studies on protein expression of AKT isoforms particularly AKT-1 and -2 and the mechanism of post-transcriptional regulation of AKT isoforms in OSCC are now undertaken.

This study was supported by Intramural Research Grant, Faculty of Dentistry, Chiang Mai University, Thailand.