An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/- mice.
basic_science · Level V
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- Record sourced from PubMed, PMID 11504907.
- Also identified by PMC identifier 56959.
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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.
Medical subject headings
- Phosphoric Monoester Hydrolases
- Protein Kinase Inhibitors
- Protein Kinases
- Ribosomal Protein S6 Kinases
- Tumor Suppressor Proteins