mTOR Complex 2 Is Required for the Development of Prostate Cancer Induced by Pten Loss in Mice

Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
Cancer cell (Impact Factor: 23.89). 03/2009; 15(2):148-59. DOI: 10.1016/j.ccr.2008.12.017
Source: PubMed

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.

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Available from: Mark A Magnuson, Feb 11, 2014
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    • "an et al . , 2009 ) . In contrast , the role of the mTORC2 complex , which is based on the interaction between rictor ( rapamycin - insensitive companion of mTOR ) and mTOR ( Jacinto et al . , 2004 ) , has only recently emerged in cancer cell biology and is mainly related to the control of Akt S473 phosphorylation and the control of SGK activity ( Guertin et al . , 2009 ) ."
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    • ") mice have been created to establish conditional knockouts to study the selective loss of mTOR or of each complex in different tissues and cell types. Studies using these mouse lines are rapidly emerging and include loss of mTOR in muscle (Risson et al., 2009; Lang et al., 2010) or Schwann cells (Sherman et al., 2012), of raptor in liver (Sengupta et al., 2010), thymocytes (Tang et al., 2012) or the haematopoietic lineage (Hoshii et al., 2012; Kalaitzidis et al., 2012) and of rictor in muscle (Kumar et al., 2008), prostate (Guertin et al., 2009), fat (Kumar et al., 2010), neurons (Siuta et al., 2010), beta cells (Gu et al., 2010), T-cells/thymocytes (Lee et al., 2010; Tang et al., 2012), liver (Yuan et al., 2012), the haematopoietic lineage (Kalaitzidis et al., 2012) or neural progenitor cells (Carson et al., 2013). These studies demonstrate the wide importance for the mTOR complexes in many cell systems. "
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