PTEN-mediated AKT activation contributes to the reduced apoptosis among Indian oral squamous cell carcinoma patients

Abstract

The tumor suppressor gene PTEN negatively regulates Akt, a downstream mediator phosphoinositol 3-kinase. Several studies have reported the role of PTEN gene in Akt downregulation and apoptosis induction in different cancers and cell lines. However, the role of loss of PTEN expression in Akt activation and spontaneous apoptosis in oral squamous cell carcinoma clinical specimens is not well established. We investigated the expression of PTEN and phospho-Akt in 146 formalin-fixed (archived) paraffin-embedded oral squamous cell carcinoma tissue sections through immunohistochemical analysis. Programmed cell death (apoptosis) was determined by Terminal deoxynucleotidyl Transferase Biotin-dUTP Nick End Labeling assay. Sixty-one percent loss of PTEN expression and 68.5% Akt activation was observed in oral squamous cell carcinoma. A significant correlation was found between loss of PTEN expression and Akt activation. Loss of PTEN expression and Akt activation were further correlated with different clinical parameters and found to be significantly correlated with tumor stage. Apoptotic index was estimated and correlated with PTEN expression and Akt activation. The percentage of apoptotic cells varied from 0.2 to 14.1%. Low apoptotic index was observed in 105 (72%) of samples, and it was found to be significantly related with loss of PTEN expression and phospho-Akt The present study confirms the contribution of loss of PTEN expression in Akt phosphorylation and spontaneous apoptosis suppression in the specimens of oral cancer. Both PTEN and phospho-Akt are likely to be concerned with oral cancer progression and reduced incidence of spontaneous apoptosis.