mTOR complex 2 is required for the development of prostate cancer induced by Pten loss in mice.

Guertin DA, Stevens DM, Saitoh M, Kinkel S, Crosby K, Sheen JH, Mullholland DJ, Magnuson MA, Wu H, Sabatini DM
Cancer Cell. 2009 15 (2): 148-59

PMID: 19185849 · PMCID: PMC2701381 · DOI:10.1016/j.ccr.2008.12.017

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.

MeSH Terms (27)

Animals Carrier Proteins Cells, Cultured Cell Transformation, Neoplastic Epithelial Cells Fibroblasts Humans Male Mice Mice, Inbred BALB C Mice, Nude Neoplasm Transplantation Phenotype Phosphotransferases (Alcohol Group Acceptor) Prostate Prostatic Neoplasms Protein-Serine-Threonine Kinases Protein Kinases Proto-Oncogene Proteins c-akt PTEN Phosphohydrolase Pyruvate Dehydrogenase Acetyl-Transferring Kinase Rapamycin-Insensitive Companion of mTOR Protein RNA Interference Signal Transduction TOR Serine-Threonine Kinases Transcription Factors Transplantation, Heterologous

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