mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice
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 requir...
| Main Authors: | , , , , , , , , , |
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| Other Authors: | |
| Format: | Article |
| Language: | en_US |
| Published: |
Elsevier B.V.
2015
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| Online Access: | http://hdl.handle.net/1721.1/96802 https://orcid.org/0000-0002-1446-7256 |
| _version_ | 1826212846683291648 |
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| author | 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 Stevens, Deanna M. |
| author2 | Whitehead Institute for Biomedical Research |
| author_facet | Whitehead Institute for Biomedical Research 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 Stevens, Deanna M. |
| author_sort | Guertin, David A. |
| collection | MIT |
| description | 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. |
| first_indexed | 2024-09-23T15:38:51Z |
| format | Article |
| id | mit-1721.1/96802 |
| institution | Massachusetts Institute of Technology |
| language | en_US |
| last_indexed | 2024-09-23T15:38:51Z |
| publishDate | 2015 |
| publisher | Elsevier B.V. |
| record_format | dspace |
| spelling | mit-1721.1/968022022-10-02T03:07:26Z mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice 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 Stevens, Deanna M. Whitehead Institute for Biomedical Research Koch Institute for Integrative Cancer Research at MIT Guertin, David A. Stevens, Deanna M. Saitoh, Maki Kinkel, Stephanie Sheen, Joon-Ho Sabatini, David M. 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. W. M. Keck Foundation Damon Runyon Cancer Research Foundation (Research Fellowship) Leukemia & Lymphoma Society of America (Career Development Award) Howard Hughes Medical Institute (Investigator) National Institutes of Health (U.S.) (K99 CA1296613-01A1) National Institutes of Health (U.S.) (R01 CA107166) National Institutes of Health (U.S.) (R01 AI04389) National Institutes of Health (U.S.) (R01 CA103866) 2015-04-24T18:55:24Z 2015-04-24T18:55:24Z 2009-02 2008-10 Article http://purl.org/eprint/type/JournalArticle 15356108 http://hdl.handle.net/1721.1/96802 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. https://orcid.org/0000-0002-1446-7256 en_US http://dx.doi.org/10.1016/j.ccr.2008.12.017 Cancer Cell 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. application/pdf Elsevier B.V. Elsevier |
| spellingShingle | 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 Stevens, Deanna M. mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title | mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title_full | mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title_fullStr | mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title_full_unstemmed | mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title_short | mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice |
| title_sort | mtor complex 2 is required for the development of prostate cancer induced by pten loss in mice |
| url | http://hdl.handle.net/1721.1/96802 https://orcid.org/0000-0002-1446-7256 |
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