PMID- 19176516
OWN - NLM
STAT- MEDLINE
DCOM- 20090318
LR  - 20211203
IS  - 1937-9145 (Electronic)
IS  - 1945-0877 (Linking)
VI  - 2
IP  - 55
DP  - 2009 Jan 27
TI  - Differential requirement of mTOR in postmitotic tissues and tumorigenesis.
PG  - ra2
LID - 10.1126/scisignal.2000189 [doi]
AB  - The mammalian target of rapamycin (mTOR) is a crucial effector in a complex 
      signaling network commonly disrupted in cancer. mTOR exerts its multiple 
      functions in the context of two different multiprotein complexes: mTOR complex 1 
      (mTORC1) and mTOR complex 2 (mTORC2). Loss of the tumor suppressor PTEN 
      (phosphatase and tensin homolog deleted from chromosome 10) can hyperactivate 
      mTOR through AKT and represents one of the most frequent events in human prostate 
      cancer. We show here that conditional inactivation of mTor in the adult mouse 
      prostate is seemingly inconsequential for this postmitotic tissue. Conversely, 
      inactivation of mTor leads to a marked suppression of Pten loss-induced tumor 
      initiation and progression in the prostate. This suppression is more pronounced 
      than that elicited by the sole pharmacological abrogation of mTORC1. Acute 
      inactivation of mTor in vitro also highlights the differential requirement of 
      mTor function in proliferating and transformed cells. Collectively, our data 
      constitute a strong rationale for developing specific mTOR inhibitors targeting 
      both mTORC1 and mTORC2 for the treatment of tumors triggered by PTEN deficiency 
      and aberrant mTOR signaling.
FAU - Nardella, Caterina
AU  - Nardella C
AD  - Cancer Genetics Program, Beth Israel Deaconess Cancer Center, Department of 
      Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 
      MA 02115, USA.
FAU - Carracedo, Arkaitz
AU  - Carracedo A
FAU - Alimonti, Andrea
AU  - Alimonti A
FAU - Hobbs, Robin M
AU  - Hobbs RM
FAU - Clohessy, John G
AU  - Clohessy JG
FAU - Chen, Zhenbang
AU  - Chen Z
FAU - Egia, Ainara
AU  - Egia A
FAU - Fornari, Alessandro
AU  - Fornari A
FAU - Fiorentino, Michelangelo
AU  - Fiorentino M
FAU - Loda, Massimo
AU  - Loda M
FAU - Kozma, Sara C
AU  - Kozma SC
FAU - Thomas, George
AU  - Thomas G
FAU - Cordon-Cardo, Carlos
AU  - Cordon-Cardo C
FAU - Pandolfi, Pier Paolo
AU  - Pandolfi PP
LA  - eng
GR  - R01 CA082328/CA/NCI NIH HHS/United States
GR  - U24 CA083084/CA/NCI NIH HHS/United States
GR  - R01 MD004038/MD/NIMHD NIH HHS/United States
GR  - P30 CA08748/CA/NCI NIH HHS/United States
GR  - R01 CA-82328/CA/NCI NIH HHS/United States
GR  - U01 CA-84292/CA/NCI NIH HHS/United States
GR  - P30 CA008748/CA/NCI NIH HHS/United States
GR  - R01 CA082328-05/CA/NCI NIH HHS/United States
GR  - R01 CA082328-06/CA/NCI NIH HHS/United States
GR  - U24 CA083084-10/CA/NCI NIH HHS/United States
GR  - R01 CA082328-07/CA/NCI NIH HHS/United States
GR  - R24CA83084/CA/NCI NIH HHS/United States
GR  - R01 CA082328-12/CA/NCI NIH HHS/United States
GR  - U01 CA084292-10/CA/NCI NIH HHS/United States
GR  - U01 CA084292/CA/NCI NIH HHS/United States
GR  - U01 CA084292-06/CA/NCI NIH HHS/United States
GR  - U01 CA084292-07/CA/NCI NIH HHS/United States
GR  - U01 CA084292-08/CA/NCI NIH HHS/United States
GR  - R24 CA083084/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20090127
PL  - United States
TA  - Sci Signal
JT  - Science signaling
JID - 101465400
RN  - 0 (Carrier Proteins)
RN  - 0 (Multiprotein Complexes)
RN  - 0 (Proteins)
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 (Mechanistic Target of Rapamycin Complex 1)
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/*metabolism
MH  - Cell Line, Transformed
MH  - Cell Proliferation
MH  - Cell Transformation, Neoplastic
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Mechanistic Target of Rapamycin Complex 1
MH  - Mice
MH  - Mitosis
MH  - Models, Biological
MH  - Multiprotein Complexes
MH  - PTEN Phosphohydrolase/metabolism
MH  - Phosphotransferases (Alcohol Group Acceptor)/*metabolism
MH  - Proteins
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - TOR Serine-Threonine Kinases/*physiology
PMC - PMC2906144
MID - NIHMS211420
EDAT- 2009/01/30 09:00
MHDA- 2009/03/19 09:00
PMCR- 2010/07/19
CRDT- 2009/01/30 09:00
PHST- 2009/01/30 09:00 [entrez]
PHST- 2009/01/30 09:00 [pubmed]
PHST- 2009/03/19 09:00 [medline]
PHST- 2010/07/19 00:00 [pmc-release]
AID - 2/55/ra2 [pii]
AID - 10.1126/scisignal.2000189 [doi]
PST - epublish
SO  - Sci Signal. 2009 Jan 27;2(55):ra2. doi: 10.1126/scisignal.2000189.