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Department of Pathology and Department of Medicine, College of Physicians and Surgeons, Columbia University, New York, New York 10032 [J. L., L. S., M. T., C. M., R. P.], and Cold Spring Harbor Laboratory, Cold Spring Harbor, New York 11724 [M. P. M., N. T.]
PTEN/MMAC1 is a tumor suppressor gene that is mutated in a variety of cancers. PTEN encodes a phosphatase that recognizes phosphoprotein substrates and the phospholipid, phosphatidylinositol-3,4,5-triphosphate. PTEN inhibited cell growth and/or colony formation in all of the epithelial lines tested with one exception. The decrease in cellular proliferation was associated with an induction of apoptosis and an inhibition of signaling through the phosphatidylinositol 3'-kinase pathway. Akt/protein kinase B, a gene whose antiapoptotic function is regulated by phosphatidylinositol-3,4,5-triphosphate, was able to rescue cells from PTEN-dependent death. PTEN, therefore, appears to suppress tumor growth by regulating phosphatidylinositol 3'-kinase signaling.
1 This work was supported in part by Grant NIH PO1 CA75553 and the James S. McDonnell Foundation.
2 To whom requests for reprints should be addressed, at 630 West 168th Street, College of Physicians and Surgeons, 14-453, Columbia University, New York, NY 10032.
Received 9/ 9/98. Accepted 10/30/98.
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