Cell cycle arrest by the PTEN tumor suppressor is target cell specific andmay require protein phosphatase activity

PTEN, a tumor suppressor commonly targeted in human cancer, possesses phosp hatase activities toward both protein and lipid substrates. While PTEN supp resses gliomas through cell cycle inhibition which requires its lipid phosp hatase activity, PTEN's effects on other tumor types and the role of its pr otein phosphatase activity are controversial or unknown. Here we show that exogenous wild-type PTEN arrests some, but not all human breast cancer cell lines in G1, in a manner independent of endogenous PTEN. Unexpectedly, the G129E mutant of PTEN selectively deficient in the lipid phosphatase activi ty still blocked the cell cycle of MCF-7 cells, while the G129R and H123Y m utants lacking both phosphatase activities were ineffective. These results suggest that PTEN's protein phosphatase activity likely contributes to its tumor suppressor function in subsets of tumors and that elucidation of down stream targets which dictate cellular responses to PTEN may have important implications for future cancer treatment strategies. (C) 2000 Academic Pres s.