title: Evaluation of Akt and RICTOR Expression Levels in Astrocytomas of All Grades.
abstract: 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.
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Arthur William
authors: AW
authors: Alvarenga
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Luis Eduardo
authors: LE
authors: Machado
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Bruna Roz
authors: BR
authors: Rodrigues
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Fernanda Cristina Sulla
authors: FC
authors: Lupinacci
authors: Neurosurgery Department (PS).
authors: Paulo
authors: P
authors: Sanemastu
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Eduardo
authors: E
authors: Matta
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Martín
authors: M
authors: Roffé
authors: A.C.Camargo Cancer Center, São Paulo, Brazil, and Institute Pelé-Pequeno Príncipe for Research on Pediatric Cancer, Curitiba, Brazil (LFBT).
authors: Luís Fernando Bleggi
authors: LF
authors: Torres
authors: Pathology Department (IWC).
authors: Isabela Werneck
authors: IW
authors: da Cunha
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Vilma Regina
authors: VR
authors: Martins
authors: International Research Center (AWA, LEM, BRR, FCSL, EM, MR, VRM, GNMH).
authors: Glaucia Noeli Maroso
authors: GN
authors: Hajj
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001254:Astrocytoma / Q000473:pathology*; D001921:Brain / Q000473:pathology*; D001932:Brain Neoplasms / Q000473:pathology*; D002352:Carrier Proteins / Q000032:analysis*; D049109:Cell Proliferation; D002648:Child; D002675:Child, Preschool; D005260:Female; D005909:Glioblastoma / Q000473:pathology; D006801:Humans; D019394:Ki-67 Antigen / Q000032:analysis; D008297:Male; D008875:Middle Aged; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis*; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D055815:Young Adult
chemical_list: D002352:Carrier Proteins; D019394:Ki-67 Antigen; C492571:RICTOR protein, human; D000076226:Rapamycin-Insensitive Companion of mTOR Protein; D051057:Proto-Oncogene Proteins c-akt
keywords: Akt; RICTOR; astrocytoma; mTOR