mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice
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Guertin-2009-mTOR Complex 2 Is Re.pdf
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Author(s)
Guertin, David A.
Stevens, Deanna M.
Saitoh, Maki
Kinkel, Stephanie
Crosby, Katherine
Sheen, Joon-Ho
Mullholland, David J.
Magnuson, Mark A.
Wu, Hong
Sabatini, David
Date Issued
February 2009
Journal
Cancer Cell
Publisher
Elsevier B.V.
Citation
Guertin, David A., Deanna M. Stevens, Maki Saitoh, Stephanie Kinkel, Katherine Crosby, Joon-Ho Sheen, David J. Mullholland, Mark A. Magnuson, Hong Wu, and David M. Sabatini. “mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice.” Cancer Cell 15, no. 2 (February 2009): 148–159.© 2009 Elsevier Inc.
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Final published version
Abstract
mTOR complex 2 (mTORC2) contains the mammalian target of rapamycin (mTOR) kinase and the Rictor regulatory protein and phosphorylates Akt. Whether this function of mTORC2 is critical for cancer progression is unknown. Here, we show that transformed human prostate epithelial cells lacking PTEN require mTORC2 to form tumors when injected into nude mice. Furthermore, we find that Rictor is a haploinsufficient gene and that deleting one copy protects Pten heterozygous mice from prostate cancer. Finally, we show that the development of prostate cancer caused by Pten deletion specifically in prostate epithelium requires mTORC2, but that for normal prostate epithelial cells, mTORC2 activity is nonessential. The selective requirement for mTORC2 in tumor development suggests that mTORC2 inhibitors may be of substantial clinical utility.
MIT Department
Whitehead Institute for Biomedical Research
Koch Institute for Integrative Cancer Research at MIT
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Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use.
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DOI of Published Version
https://doi.org/10.1016/j.ccr.2008.12.017
