PMID- 27789731
OWN - NLM
STAT- MEDLINE
DCOM- 20170530
LR  - 20190306
IS  - 1551-5044 (Electronic)
IS  - 0022-1554 (Print)
IS  - 0022-1554 (Linking)
VI  - 65
IP  - 2
DP  - 2017 Feb
TI  - Evaluation of Akt and RICTOR Expression Levels in Astrocytomas of All Grades.
PG  - 93-103
LID - 10.1369/0022155416675850 [doi]
AB  - The mammalian target of rapamycin (mTOR) binds to several protein partners and 
      forms two complexes, termed mTOR complexes 1 and 2 (mTORC1/2), that differ in 
      components, substrates, and regulation. mTORC2 contains the protein 
      Rapamycin-insensitive companion of mTOR (RICTOR); phosphorylates kinases of the 
      AGC family, such as Akt; and controls the cytoskeleton. Even though the 
      regulation of mTORC2 activity remains poorly understood, the hyperactivation of 
      this signaling pathway has been shown to contribute to the oncogenic properties 
      of gliomas in experimental models. In this work, we evaluated expression and 
      phosphorylation of Akt, and expression of RICTOR and Ki-67 in 195 human 
      astrocytomas of different grades (38 cases of grade I, 49 grade II, 15 grade III, 
      and 93 grade IV) and 30 normal brains. Expression and phosphorylation of Akt 
      increased with histological grade and correlated with a worse overall survival in 
      glioblastomas (GBMs). RICTOR was overexpressed in grade I and II astrocytomas and 
      demonstrated a shift to nuclear localization in GBMs. Nuclear RICTOR was 
      associated to increased proliferation in GBMs. Our results point to an increase 
      in total and phosphorylated Akt in high-grade gliomas and to a possible role of 
      RICTOR in proliferations of high-grade GBM cells.
FAU - Alvarenga, Arthur William
AU  - Alvarenga AW
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Machado, Luis Eduardo
AU  - Machado LE
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Rodrigues, Bruna Roz
AU  - Rodrigues BR
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Lupinacci, Fernanda Cristina Sulla
AU  - Lupinacci FC
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Sanemastu, Paulo
AU  - Sanemastu P
AD  - Neurosurgery Department (PS).
FAU - Matta, Eduardo
AU  - Matta E
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Roffe, Martin
AU  - Roffe M
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Torres, Luis Fernando Bleggi
AU  - Torres LF
AD  - A.C.Camargo Cancer Center, Sao Paulo, Brazil, and Institute Pele-Pequeno Principe 
      for Research on Pediatric Cancer, Curitiba, Brazil (LFBT).
FAU - da Cunha, Isabela Werneck
AU  - da Cunha IW
AD  - Pathology Department (IWC).
FAU - Martins, Vilma Regina
AU  - Martins VR
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
FAU - Hajj, Glaucia Noeli Maroso
AU  - Hajj GN
AD  - International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20161028
PL  - United States
TA  - J Histochem Cytochem
JT  - The journal of histochemistry and cytochemistry : official journal of the 
      Histochemistry Society
JID - 9815334
RN  - 0 (Carrier Proteins)
RN  - 0 (Ki-67 Antigen)
RN  - 0 (RICTOR protein, human)
RN  - 0 (Rapamycin-Insensitive Companion of mTOR Protein)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Aged
MH  - Astrocytoma/*pathology
MH  - Brain/*pathology
MH  - Brain Neoplasms/*pathology
MH  - Carrier Proteins/*analysis
MH  - Cell Proliferation
MH  - Child
MH  - Child, Preschool
MH  - Female
MH  - Glioblastoma/pathology
MH  - Humans
MH  - Ki-67 Antigen/analysis
MH  - Male
MH  - Middle Aged
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*analysis
MH  - Rapamycin-Insensitive Companion of mTOR Protein
MH  - Young Adult
PMC - PMC5256195
OTO - NOTNLM
OT  - Akt
OT  - RICTOR
OT  - astrocytoma
OT  - mTOR
COIS- The author(s) declared no potential conflicts of interest with respect to the 
      research, authorship, and/or publication of this article.
EDAT- 2016/11/01 06:00
MHDA- 2017/05/31 06:00
PMCR- 2018/02/01
CRDT- 2016/11/01 06:00
PHST- 2016/11/01 06:00 [pubmed]
PHST- 2017/05/31 06:00 [medline]
PHST- 2016/11/01 06:00 [entrez]
PHST- 2018/02/01 00:00 [pmc-release]
AID - 0022155416675850 [pii]
AID - 10.1369_0022155416675850 [pii]
AID - 10.1369/0022155416675850 [doi]
PST - ppublish
SO  - J Histochem Cytochem. 2017 Feb;65(2):93-103. doi: 10.1369/0022155416675850. Epub 
      2016 Oct 28.