The Tumor Suppressor Gene PTEN Plays a Role in Cell Cycle Regulation and Apoptosis in Prostate Cancer Cell Lines

Abstract

SummaryPhosphatase and tension homology deleted on chromosome ten (PTEN) is a tumor suppressor gene with protein and lipid phosphatase activity frequently altered in several types of human cancers. Herein, we demonstrate the effect of transfected wild type (wt) PTEN and its mutants (mt) L57W, H123Y, G129R that have lost lipid and protein phosphatase activity; and G129E characterized by loss of only lipid phosphatase activity, during the cell cycle and on apoptosis. We characterized the expression of important proteins regulating the cell cycle and the PI3-K/PKB/Akt pathway, analyzed PTEN cellular localization, and performed PTEN mutation analysis in DU-145 and PC-3 cells. The transfection of wt PTEN and its mt with defective lipid phosphatase activity (G129E) inhibited S-phase entry of DU-145 and PC-3 cells. In DU-145 cells, transfection of wt PTEN induced apoptosis. An inverse expression of PTEN and phosphorylated PKB/Akt was observed. We did not find any mutations of the PTEN gene in either cell line. PTEN influenced the cell cycle of tested cells in a p53 and pRb independent manner, and the effect was cell type specific.