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Proc Natl Acad Sci U S A. 2001 Aug 28;98(18):10320-5. Epub 2001 Aug 14.

An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice.

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  • 1Institute of Cancer Genetics, Department of Pathology and Medicine, College of Physicians and Surgeons, Columbia University, 1150 St. Nicholas Avenue, Russ Berrie Pavilion, New York, NY 10032, USA.


PTEN phosphatase acts as a tumor suppressor by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downstream components of this pathway are necessary for oncogenic transformation. In this report we show that transformed cells of PTEN(+/-) mice have elevated levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FRAP reduced neoplastic proliferation, tumor size, and p70/S6 kinase activity, but did not affect the status of Akt. These data suggest that p70/S6K and possibly other targets of mTOR contribute significantly to tumor development and that inhibition of these proteins may be therapeutic for cancer patients with deranged PI3K signaling.

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