[PTEN induces apoptosis and up-regulates p53 expression in HepG2 cells].
OBJECTIVE
To investigate the effects of tumor suppressor gene PTEN on apoptosis and protein expression of p53 in HepG2 cells, as well as to explore its mechanisms.


METHODS
HepG2 cells were transfected with GFP plasmids containing wild-type PTEN or G129E-PTEN and C124A-PTEN in vitro. Both the expression of wild-type p53 and the phosphorylation of protein kinase B (PKB/Akt) and focal adhesion kinase (FAK) were detected by Western blotting. Flow cytometry and confocal microscopy were used to analyze apoptosis of the transfected cells.


RESULTS
Compared with the control, the expression of phosphorylated FAK and phosphoylated Akt were down-regulated in HepG2 cells transfected with wild-type PTEN (-65%, -93%) and G129E-PTEN (-65%, -35%), whereas the apoptosis percentage increased to (19.8+/-1.2)% and (9.2+/-0.6)%, and p53 expression was up-regulated by 120% and 50%, respectively. However, in the cells transfected with C124A-PTEN, neither the phosphorylation of FAK and Akt nor the apoptosis percentage and p53 expression had changed.


CONCLUSIONS
PTEN can dephosphrylate FAK through its protein phosphatase activity, and suppress phosphorylation of Akt mainly through its lipid phosphatase activity. Consequently, it can induce apoptosis of HepG2 cells and up-regulate p53 expression.
Yang
Zhi-Fang
ZF
Department of Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Yi
Ji-Lin
JL
Li
Xing-Rui
XR
Xie
Da-Xing
DX
Liao
Xiao-Feng
XF
Ma
Xin
X
D017209:Apoptosis / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D051059:PTEN Phosphohydrolase / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D015854:Up-Regulation
D016159:Tumor Suppressor Protein p53; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human