PMID- 19185849
OWN - NLM
STAT- MEDLINE
DCOM- 20090227
LR  - 20240417
IS  - 1878-3686 (Electronic)
IS  - 1535-6108 (Print)
IS  - 1535-6108 (Linking)
VI  - 15
IP  - 2
DP  - 2009 Feb 3
TI  - mTOR complex 2 is required for the development of prostate cancer induced by Pten 
      loss in mice.
PG  - 148-59
LID - 10.1016/j.ccr.2008.12.017 [doi]
AB  - 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.
FAU - Guertin, David A
AU  - Guertin DA
AD  - Whitehead Institute for Biomedical Research, Cambridge, MA 02142, USA.
FAU - Stevens, Deanna M
AU  - Stevens DM
FAU - Saitoh, Maki
AU  - Saitoh M
FAU - Kinkel, Stephanie
AU  - Kinkel S
FAU - Crosby, Katherine
AU  - Crosby K
FAU - Sheen, Joon-Ho
AU  - Sheen JH
FAU - Mullholland, David J
AU  - Mullholland DJ
FAU - Magnuson, Mark A
AU  - Magnuson MA
FAU - Wu, Hong
AU  - Wu H
FAU - Sabatini, David M
AU  - Sabatini DM
LA  - eng
GR  - R01 AI04389/AI/NIAID NIH HHS/United States
GR  - R01 AI047389-05/AI/NIAID NIH HHS/United States
GR  - HHMI/Howard Hughes Medical Institute/United States
GR  - K99 CA129613-01A1/CA/NCI NIH HHS/United States
GR  - R01 AI047389/AI/NIAID NIH HHS/United States
GR  - R01 CA103866/CA/NCI NIH HHS/United States
GR  - K99 CA129613/CA/NCI NIH HHS/United States
GR  - R01 CA103866-05/CA/NCI NIH HHS/United States
GR  - R01 CA107166/CA/NCI NIH HHS/United States
GR  - K99 CA1296613-01A1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cancer Cell
JT  - Cancer cell
JID - 101130617
RN  - 0 (Carrier Proteins)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - 0 (Transcription Factors)
RN  - 0 (rictor protein, mouse)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
RN  - EC 3.1.3.67 (PTEN Phosphohydrolase)
RN  - EC 3.1.3.67 (Pten protein, mouse)
SB  - IM
MH  - Animals
MH  - Carrier Proteins/genetics/*metabolism
MH  - Cell Transformation, Neoplastic
MH  - Cells, Cultured
MH  - Epithelial Cells/pathology/physiology
MH  - Fibroblasts/cytology/physiology
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Nude
MH  - Neoplasm Transplantation
MH  - PTEN Phosphohydrolase/genetics/*metabolism
MH  - Phenotype
MH  - Phosphotransferases (Alcohol Group Acceptor)/genetics/*metabolism
MH  - Prostate/cytology/metabolism/pathology
MH  - Prostatic Neoplasms/pathology/*physiopathology
MH  - Protein Kinases/genetics/*metabolism
MH  - Protein Serine-Threonine Kinases/genetics/metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
MH  - RNA Interference
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases
MH  - Transcription Factors/genetics/*metabolism
MH  - Transplantation, Heterologous
PMC - PMC2701381
MID - NIHMS95153
EDAT- 2009/02/03 09:00
MHDA- 2009/02/28 09:00
PMCR- 2009/08/03
CRDT- 2009/02/03 09:00
PHST- 2008/06/27 00:00 [received]
PHST- 2008/10/22 00:00 [revised]
PHST- 2008/12/18 00:00 [accepted]
PHST- 2009/02/03 09:00 [entrez]
PHST- 2009/02/03 09:00 [pubmed]
PHST- 2009/02/28 09:00 [medline]
PHST- 2009/08/03 00:00 [pmc-release]
AID - S1535-6108(08)00436-4 [pii]
AID - 10.1016/j.ccr.2008.12.017 [doi]
PST - ppublish
SO  - Cancer Cell. 2009 Feb 3;15(2):148-59. doi: 10.1016/j.ccr.2008.12.017.