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- Title
Complex interactions between the components of the PI3K/AKT/mTOR pathway, and with components of MAPK, JAK/STAT and Notch-1 pathways, indicate their involvement in meningioma development.
- Authors
El-Habr, Elias; Levidou, Georgia; Trigka, Eleni-Andriana; Sakalidou, Joanna; Piperi, Christina; Chatziandreou, Ilenia; Spyropoulou, Anastasia; Soldatos, Rigas; Tomara, Georgia; Petraki, Kalliopi; Samaras, Vassilis; Zisakis, Athanasios; Varsos, Vassilis; Vrettakos, George; Boviatsis, Efstathios; Patsouris, Efstratios; Saetta, Angelica; Korkolopoulou, Penelope
- Abstract
We investigated the significance of PI3K/AKT/mTOR pathway and its interactions with MAPK, JAK/STAT and Notch pathways in meningioma progression. Paraffin-embedded tissue from 108 meningioma patients was analysed for the presence of mutations in PIK3CA and AKT1. These were correlated with the expression status of components of the PI3K/AKT/mTOR pathway, including p85α and p110γ subunits of PI3K, phosphorylated (p)-AKT, p-mTOR, p-p70S6K and p-4E-BP1, as well as of p-ERK1/2, p-STAT3 and Notch-1, clinicopathological data and patient survival. A mutation in PIK3CA or AKT1 was found in around 9 % of the cases. Higher grade meningiomas displayed higher nuclear expression of p-p70S6K; higher nuclear and cytoplasmic expression of p-4E-BP1 and of Notch-1; lower cytoplasmic expression of p85αPI3K, p-p70S6K and p-ERK1/2; and lower PTEN Histo-scores (H-scores). PTEN H-score was inversely correlated with recurrence probability. In univariate survival analysis, nuclear expression of p-4E-BP1 and absence of p-ERK1/2 expression portended adverse prognosis, whereas in multivariate survival analysis, p-ERK1/2 expression emerged as an independent favourable prognostic factor. Treatment of the human meningioma cell line HBL-52 with the PI3K inhibitor LY294002 resulted in reduction of p-AKT, p-p70S6K and p-ERK1/2 protein levels. The complex interactions established between components of the PI3K/AKT/mTOR pathway, or with components of the MAPK, JAK/STAT and Notch-1 pathways, appear to be essential for facilitating and fuelling meningioma progression.
- Subjects
MENINGIOMA; BRAIN tumors; CEREBELLAR tumors; METASTASIS; SUPRATENTORIAL brain tumors
- Publication
Virchows Archiv: European Journal of Pathology, 2014, Vol 465, Issue 4, p473
- ISSN
0945-6317
- Publication type
Article
- DOI
10.1007/s00428-014-1641-3