It was to study whether overexpression of the tumor suppressor PTEN in HEK293 cells could lead to apoptosis and cell cycle arrest. The wild-type and mutant T910G of PTEN expression plasmids were constructed and transfected into PTEN-null HEK293 cells respectively. Apoptosis was evaluated by the appearance of cytosolic low molecular DNA ladder on the gel. Cell cycle was determined by flow-cytometric analysis. The Western blot analysis was performed to determine the phosphorylation levels of PKB/Akt and MAPK. The present data showed that the overexpression of PTEN in HEK293 cells could induce apoptosis and resulted in an increase in G1 cell population through inhibiting PKB/Akt and MAPK phosphrylation stimulated by PDGF. Mutant PTEN cause less apoptosis and G1 arrest than wild-type PTEN. MAPK dephosphorylation caused by mutant PTEN was not so significant as by wild-type PTEN. These data suggested that PTEN may exert its tumor-suppressive effects through both the inhibition of cell cycle progression and the induction of apoptosis.