<i>PTEN</i>Inhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/<i>hTERT</i>Pathway in Lung Adenocarcinoma A549 Cells

Abstract

<i>PTEN</i> plays an essential role in tumorigenesis and both its mutation and inactivation can influence proliferation, apoptosis, and cell cycle progression in tumor cells. However, the precise role of <i>PTEN</i> in lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutant <i>PTEN</i> as well as A549 cells expressing a siRNA directed toward endogenous <i>PTEN</i>. Overexpression of wild-type <i>PTEN</i> profoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase protein <i>hTERT</i>. In contrast, in cells expressing a <i>PTEN</i> directed siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, and <i>hTERT</i> protein expression were observed. A549 cells transfected with a <i>PTEN</i> mutant lacking phosphatase activity (<i>PTEN</i>-C124A) or an empty vector (null) did not show any effect. Furthermore, using the PI3K/AKT pathway blocker LY294002, we confirmed that the PI3K/AKT pathway was involved in mediating these effects of <i>PTEN</i>. Taken together, we have demonstrated that <i>PTEN</i> downregulates the PI3K/AKT/<i>hTERT</i> pathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.