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Akt2 and Akt3 play a pivotal role in malignant gliomas.

Authors: Mure, Hideo  Matsuzaki, Kazuhito  Kitazato, Keiko T  Mizobuchi, Yoshifumi  Kuwayama, Kazuyuki  Kageji, Teruyoshi  Nagahiro, Shinji 
Citation: Mure H, etal., Neuro Oncol. 2010 Mar;12(3):221-32. doi: 10.1093/neuonc/nop026. Epub 2009 Dec 21.
Pubmed: (View Article at PubMed) PMID:20167810
DOI: Full-text: DOI:10.1093/neuonc/nop026

Akt, one of the major downstream effectors of phosphatidylinositol 3-kinase, is hyper-expressed and activated in a variety of cancers including glioblastoma. However, the expression profiles of the Akt isoforms Akt1/PKBalpha, Akt2/PKBbeta, and Akt3/PKBgamma and their functional roles in malignant glioma are not well understood. Therefore, we examined the protein and mRNA expression patterns of Akt isoforms in tissues from human astrocytomas, glioblastomas, and non-neoplastic regions. We also explored the biological role of each Akt isoform in malignant glioma cells using RNA interference-mediated knock-down and the over-expression of plasmid DNA of each isoform. The expression of Akt1 protein and mRNA was similar in glioma and normal control tissues. Although the protein and mRNA level of Akt2 increased with the pathological grade of malignancy, the expression of Akt3 mRNA and protein decreased as the malignancy grade increased. In U87MG, T98G, and TGB cells, the down-regulation of Akt2 or Akt3 by RNA interference reduced the expression of the phosphorylated form of Bad, resulting in the induction of caspase-dependent apoptosis. Akt1 knock-down did not affect cell growth or survival. We first demonstrate that the over-expression of Akt2 or Akt3 down-regulated the expression of the other protein and that endogenous Akt3 protein showed high kinase activity in U87MG cells. Our data suggest that Akt2 and Akt3 play an important role in the viability of human malignant glioma cells. Targeting Akt2 and Akt3 may hold promise for the treatment of patients with gliomas.

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CRRD Object Information
CRRD ID: 13674163
Created: 2018-07-10
Species: All species
Last Modified: 2018-07-10
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.