AKT activation and telomerase reverse transcriptase expression are concurrently associated with prognosis of gastric cancer.

Abstract

AKT is a protein in the phosphatidylinositol-3 kinase (PI3K) pathway and associated with diverse pro-tumoral responses. Activation of the human telomere reverse transcriptase (hTERT) is one of AKT's tumorigenic effects. In this study, the significance of AKT phosphorylation and hTERT on prognosis of gastric cancer were examined. AKT activation by epidermal growth factor increased hTERT expression and telomerase activity. In contrast, AKT inactivation by inhibitors and knockdown decreased hTERT expression and telomerase activity in MKN28 gastric cancer cells. In 40 gastric cancer tissues, significant correlations were found among the levels of phosphorylated AKT (pAKT), hTERT expression, and telomer length. The pAKT levels or the levels of pAKT/hTERT were not associated with clinicopathological parameters, including stage and nodal metastasis. However, survival rates of the pAKT-high patients or the pAKT-high and hTERT-high patients were significantly poorer than those in other patients. These findings suggest that AKT and hTERT are good molecular targets for the treatment of gastric cancer.