An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/− mice
AUTOR(ES)
Podsypanina, Katrina
FONTE
The National Academy of Sciences
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=56959Documentos Relacionados
- mTor is required for hypertrophy of Pten-deficient neuronal soma in vivo
- A role of the kinase mTOR in cellular transformation induced by the oncoproteins P3k and Akt
- Characterization of Rictor Phosphorylation Sites Reveals Direct Regulation of mTOR Complex 2 by S6K1▿ †
- REDD1, an inhibitor of mTOR signalling, is regulated by the CUL4A–DDB1 ubiquitin ligase
- Human Cytomegalovirus Infection Induces Rapamycin-Insensitive Phosphorylation of Downstream Effectors of mTOR Kinase