Department of Gastroenterolgical Surgery, Fukuoka University School of Medicine, Fukuoka, Japan.
Pathobiology. 2014;81(1):36-41. doi: 10.1159/000351721. Epub 2013 Aug 21.
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.
AKT 是磷脂酰肌醇-3 激酶（PI3K）通路中的一种蛋白，与多种促肿瘤反应有关。人端粒酶逆转录酶（hTERT）的激活是 AKT 的致癌作用之一。在这项研究中，检测了 AKT 磷酸化和 hTERT 对胃癌预后的意义。表皮生长因子激活 AKT 增加了 hTERT 的表达和端粒酶活性。相反，抑制剂和敲低 AKT 降低了 MKN28 胃癌细胞中的 hTERT 表达和端粒酶活性。在 40 例胃癌组织中，发现磷酸化 AKT（pAKT）、hTERT 表达和端粒长度之间存在显著相关性。pAKT 水平或 pAKT/hTERT 水平与包括分期和淋巴结转移在内的临床病理参数无关。然而，pAKT 高患者或 pAKT 高和 hTERT 高患者的生存率明显低于其他患者。这些发现表明，AKT 和 hTERT 是治疗胃癌的良好分子靶点。
