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

Overview

MeSH Major

  • Phosphoric Monoester Hydrolases
  • Protein Kinase Inhibitors
  • Protein Kinases
  • Ribosomal Protein S6 Kinases
  • Tumor Suppressor Proteins

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.

publication date

  • August 28, 2001

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC56959

Digital Object Identifier (DOI)

  • 10.1073/pnas.171060098

PubMed ID

  • 11504907

Additional Document Info

start page

  • 10320

end page

  • 5

volume

  • 98

number

  • 18