PMID- 23307788
OWN - NLM
STAT- MEDLINE
DCOM- 20130319
LR  - 20211203
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Print)
IS  - 0013-7227 (Linking)
VI  - 154
IP  - 2
DP  - 2013 Feb
TI  - Combined inhibition of mTORC1 and mTORC2 signaling pathways is a promising 
      therapeutic option in inhibiting pheochromocytoma tumor growth: in vitro and in 
      vivo studies in female athymic nude mice.
PG  - 646-55
LID - 10.1210/en.2012-1854 [doi]
AB  - Several lines of evidence, including the recent discovery of novel susceptibility 
      genes, point out an important role for the mammalian target of rapamycin (mTOR) 
      signaling pathway in the development of pheochromocytoma. Analyzing a set of 
      pheochromocytomas from patients with different genetic backgrounds, we observed 
      and confirmed a significant overexpression of key mTOR complex (mTORC) signaling 
      mediators. Using selective ATP-competitive inhibitors targeting both mTORC1 and 
      mTORC2, we significantly arrested the in vitro cell proliferation and blocked 
      migration of pheochromocytoma cells as a result of the pharmacological 
      suppression of the Akt/mTOR signaling pathway. Moreover, AZD8055, a selective 
      ATP-competitive dual mTORC1/2 small molecular inhibitor, significantly reduced 
      the tumor burden in a model of metastatic pheochromocytoma using female athymic 
      nude mice. This study suggests that targeting both mTORC1 and mTORC2 is a 
      potentially rewarding strategy and supports the application of selective 
      inhibitors in combinatorial drug regimens for metastatic pheochromocytoma.
FAU - Giubellino, Alessio
AU  - Giubellino A
AD  - Program in Reproductive and Adult Endocrinology, Eunice Kennedy Shriver National 
      Institute of Child Health and Human Development, National Institutes of Health, 
      Bethesda, MD 20892, USA.
FAU - Bullova, Petra
AU  - Bullova P
FAU - Nolting, Svenja
AU  - Nolting S
FAU - Turkova, Hana
AU  - Turkova H
FAU - Powers, James F
AU  - Powers JF
FAU - Liu, Qingsong
AU  - Liu Q
FAU - Guichard, Sylvie
AU  - Guichard S
FAU - Tischler, Arthur S
AU  - Tischler AS
FAU - Grossman, Ashley B
AU  - Grossman AB
FAU - Pacak, Karel
AU  - Pacak K
LA  - eng
GR  - Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, U.S. Gov't, Non-P.H.S.
DEP - 20130110
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 
      (1-(4-(4-propionylpiperazin-1-yl)-3-(trifluoromethyl)phenyl)-9-(quinolin-3-yl)benzo(h)(1,6)naphthyridin-2(1H)-one)
RN  - 0 (Morpholines)
RN  - 0 (Naphthyridines)
RN  - 970JJ37FPW 
      ((5-(2,4-bis((3S)-3-methylmorpholin-4-yl)pyrido(2,3-d)pyrimidin-7-yl)-2-methoxyphenyl)methanol)
RN  - EC 2.7.1.1 (MTOR protein, human)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Adrenal Gland Neoplasms/drug therapy/pathology
MH  - Animals
MH  - Cell Movement/drug effects
MH  - Cell Proliferation/drug effects
MH  - Female
MH  - Mice
MH  - Mice, Nude
MH  - Morpholines/pharmacology
MH  - Naphthyridines/pharmacology
MH  - Pheochromocytoma/drug therapy/secondary
MH  - Signal Transduction/drug effects
MH  - TOR Serine-Threonine Kinases/*antagonists & inhibitors
PMC - PMC3548182
EDAT- 2013/01/12 06:00
MHDA- 2013/03/21 06:00
PMCR- 2014/02/01
CRDT- 2013/01/12 06:00
PHST- 2013/01/12 06:00 [entrez]
PHST- 2013/01/12 06:00 [pubmed]
PHST- 2013/03/21 06:00 [medline]
PHST- 2014/02/01 00:00 [pmc-release]
AID - en.2012-1854 [pii]
AID - EN-12-1854 [pii]
AID - 10.1210/en.2012-1854 [doi]
PST - ppublish
SO  - Endocrinology. 2013 Feb;154(2):646-55. doi: 10.1210/en.2012-1854. Epub 2013 Jan 
      10.