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The Inducible Expression of the Tumor Suppressor Gene PTEN Promotes Apoptosis and Decreases Cell Size by Inhibiting the PI3K/Akt Pathway in Jurkat T Cells¹

Departments of Medicine and of Microbiology and Immunology and the Howard Hughes Medical Institute, University of California, San Francisco, California 94143-0795 [Z. X., L. P. K., A. W.], and Cancer Research Institute, University of California, San Francisco, California 94115 [D. S.]

In this study, we characterize the function of the tumor suppressor gene PTEN in Jurkat T cells. We established stable clones of Jurkat T cells that inducibly express either wild-type or phosphatase-inactive PTEN. We show here that PTEN potently inhibited the growth and reduced the size of Jurkat cells. The growth-suppressive effect of PTEN was associated with its ability to induce apoptotic cell death with little or no effect on cell cycle. PTEN also rendered Jurkat cells more susceptible to apoptosis induced by various stimuli. Furthermore, PTEN expression led to a reduction in the level of 3'-phosphorylated phospholipids and thus altered the activity and localization of Akt. Finally, coexpression of constitutively active Akt reversed the effects caused by PTEN. In summary, our results suggest that PTEN suppresses cell growth, promotes apoptosis, and decreases cell size by negatively regulating the phosphoinositide 3-kinase/Akt pathway in Jurkat T cells.

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