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

作者：Podsypanina K; Lee RT; Politis C; Hennessy I; Crane A; Puc J; Neshat M; Wang H; Yang L; Gibbons J; Frost P; Drei**ach V; Blenis J; Gaciong Z; Fisher P; Sawyers C; Hedrick Ellenson L; Parsons R^*

来源：Proceedings of the National Academy of Sciences, 2001, 98(18): 10320-10325.

DOI：10.1073/pnas.171060098

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.

• 出版日期2001-8-28