• Media type: E-Article
  • Title: An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity inPten+/−mice
  • Contributor: Podsypanina, Katrina; Lee, Richard T.; Politis, Chris; Hennessy, Ian; Crane, Allison; Puc, Janusz; Neshat, Mehran; Wang, Hong; Yang, Lin; Gibbons, Jay; Frost, Phil; Dreisbach, Valley; Blenis, John; Gaciong, Zbigniew; Fisher, Peter; Sawyers, Charles; Hedrick-Ellenson, Lora; Parsons, Ramon
  • Published: Proceedings of the National Academy of Sciences, 2001
  • Published in: Proceedings of the National Academy of Sciences, 98 (2001) 18, Seite 10320-10325
  • Language: English
  • DOI: 10.1073/pnas.171060098
  • ISSN: 0027-8424; 1091-6490
  • Origination:
  • Footnote:
  • Description: 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.
  • Access State: Open Access