Evaluation of Akt and RICTOR Expression Levels in Astrocytomas of All Grades.

The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 2017 Feb

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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.

Citation

Arthur William Alvarenga, Luis Eduardo Machado, Bruna Roz Rodrigues, Fernanda Cristina Sulla Lupinacci, Paulo Sanemastu, Eduardo Matta, Martín Roffé, Luís Fernando Bleggi Torres, Isabela Werneck da Cunha, Vilma Regina Martins, Glaucia Noeli Maroso Hajj. Evaluation of Akt and RICTOR Expression Levels in Astrocytomas of All Grades. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society. 2017 Feb;65(2):93-103