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An inhibitor of mTOR reduces neoplasia and normalizes p70/S6 kinase activity in Pten+/−mice
Open accessAbstract
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.
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Self-citation
Metadata
- Authors
- Podsypanina, K., Lee, R. T., Politis, C., Hennessy, I., Crane, A., Puc, J., Neshat, M., Wang, H., Yang, L., Gibbons, J., Frost, P., Dreisbach, V., Blenis, J., Gaciong, Z., Fisher, P., Sawyers, C., Hedrick-Ellenson, L., & Parsons, R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-08-14
- Volume
- 98
- Issue
- 18
- Pages
- 10320-10325
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W1988609792
- Cited by
- 569
- References
- 2
- FWCI
- 18.13
- Type
- journal article
- Language
- en
- Open access
- green
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