An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity inPten+/−mice

• DOI: 10.1073/pnas.171060098
• Publication Date: 2002-07-26T14:37:36Z
• Authors: Katrina Podsypanina; Richard T. Lee; Chris Politis; Ian Hennessy; Allison Crane; Janusz Puc; Mehran Neshat; Hong Wang; Lin Yang; Jay Gibbons; Phil Frost; Valley Dreisbach; John Blenis; Zbigniew Gaciong; Peter Fisher; Charles Sawyers; Lora Hedrick-Elle...; Ramon Parsons
• Keywords: RPTOR

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 report we show that transformed cells +/− mice have elevated levels phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation mTOR/RAFT/FRAP reduced neoplastic proliferation, size, activity, but did not affect status Akt. These data suggest p70/S6K possibly other targets mTOR contribute significantly to development inhibition these proteins may be therapeutic cancer patients deranged PI3K signaling.