PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells

Abstract

PTENplays 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 ofPTENin lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutantPTENas well as A549 cells expressing a siRNA directed toward endogenousPTEN. Overexpression of wild-typePTENprofoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase proteinhTERT. In contrast, in cells expressing aPTENdirected siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, andhTERTprotein expression were observed. A549 cells transfected with aPTENmutant lacking phosphatase activity (PTEN-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 ofPTEN. Taken together, we have demonstrated thatPTENdownregulates the PI3K/AKT/hTERTpathway, thereby suppressing the growth of lung adenocarcinoma cells. Our study may provide evidence for a promising therapeutic target for the treatment of lung adenocarcinoma.