An inhibitor of mTOR reduces neoplasia and normalizes p70/s6 kinase activity in Pten+/- mice

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-Ellenson, Ramon Parsons

Research output: Contribution to journalArticlepeer-review

562 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)10320-10325
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume98
Issue number18
DOIs
StatePublished - 28 Aug 2001
Externally publishedYes

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