Abstract
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
in lung cancer cells has not been well studied. To address this, we have generated lung adenocarcinoma A549 cells overexpressing wild-type or mutant
as well as A549 cells expressing a siRNA directed toward endogenous
. Overexpression of wild-type
profoundly inhibited cell proliferation, promoted cell apoptosis, caused cell cycle arrest at G1, downregulated p-AKT, and decreased expression of the telomerase protein
. In contrast, in cells expressing a
directed siRNA, the opposite effects on cell proliferation, apoptosis, cell cycle arrest, p-AKT levels, and
protein expression were observed. A549 cells transfected with a
mutant lacking phosphatase activity (
-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
. Taken together, we have demonstrated that
downregulates the PI3K/AKT/
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.
