PTENInhibits Cell Proliferation, Promotes Cell Apoptosis, and Induces Cell Cycle Arrest via Downregulating the PI3K/AKT/hTERTPathway in Lung Adenocarcinoma A549 Cells.
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.
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Xiao-Xiao
0000-0001-8972-431X
XX
Lu
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Lan-Yu
LY
Cao
Department of Respiratory Medicine, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Xi
X
Chen
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Jian
J
Xiao
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Yong
Y
Zou
Department of Geriatrics, Xiangya Hospital of Central South University, Changsha, Hunan 410008, China.
Qiong
0000-0002-2534-8834
Q
Chen
D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D019943:Amino Acid Substitution; D017209:Apoptosis; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D002867:Chromones / Q000494:pharmacology; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009025:Morpholines / Q000494:pharmacology; D020125:Mutation, Missense; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism*
D002867:Chromones; D009025:Morpholines; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; C509186:TERT protein, human; D019098:Telomerase; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human