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

PTEN phosphatase acts as a tumor suppressor by negatively regulating the ph osphoinositide 3-kinase (PI3K) signaling pathway. It is unclear which downs tream components of this pathway are necessary for oncogenic transformation . In this report we show that transformed cells of PTEN+/- mice have elevat ed levels of phosphorylated Akt and activated p70/S6 kinase associated with an increase in proliferation. Pharmacological inactivation of mTOR/RAFT/FR AP 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 developme nt and that inhibition of these proteins may be therapeutic for cancer pati ents with deranged PI3K signaling.