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Discrepancy Between Low Levels of mTOR Activity and High Levels of P-S6 in Primary Central Nervous System Lymphoma May Be Explained by PAS Domain-Containing Serine/Threonine-Protein Kinase-Mediated Phosphorylation.
Marosvári, Dóra; Nagy, Noémi; Kriston, Csilla; Deák, Beáta; Hajdu, Melinda; Bödör, Csaba; Csala, Irén; Bagó, Attila G; Szállási, Zoltán; Sebestyén, Anna; Reiniger, Lilla.
Afiliación
  • Marosvári D; 1st Department of Pathology and Experimental Cancer Research Semmelweis University, Budapest, Hungary.
  • Nagy N; MTA-SE Lendulet Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
  • Kriston C; 1st Department of Pathology and Experimental Cancer Research Semmelweis University, Budapest, Hungary.
  • Deák B; 1st Department of Pathology and Experimental Cancer Research Semmelweis University, Budapest, Hungary.
  • Hajdu M; National Institute of Oncology, Budapest, Hungary.
  • Bödör C; 1st Department of Pathology and Experimental Cancer Research Semmelweis University, Budapest, Hungary.
  • Csala I; 1st Department of Pathology and Experimental Cancer Research Semmelweis University, Budapest, Hungary.
  • Bagó AG; MTA-SE Lendulet Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary.
  • Szállási Z; Institute of Behavioural Sciences, Semmelweis University, Budapest, Hungary.
  • Sebestyén A; Department of Neurooncology, National Institute of Clinical Neurosciences, Budapest, Hungary.
  • Reiniger L; Computational Health Informatics Program, Boston Children's Hospital, Boston, Massachusetts, Harvard Medical School, and Department of Bio and Health Informatics, Technical University of Denmark, Lyngby, Denmark.
J Neuropathol Exp Neurol ; 77(4): 268-273, 2018 04 01.
Article en En | MEDLINE | ID: mdl-29361117
The primary aim of this study was to determine mTOR-pathway activity in primary central nervous system lymphoma (PCNSL), which could be a potential target for therapy. After demonstrating that p-S6 positivity largely exceeded mTOR activity, we aimed to identify other pathways that may lead to S6 phosphorylation. We measured mTOR activity with immunohistochemistry for p-mTOR and its downstream effectors p(T389)-p70S6K1, p-S6, and p-4E-BP1 in 31 cases of PCNSL and 51 cases of systemic diffuse large B-cell lymphoma (DLBCL) and evaluated alternative S6 phosphorylation pathways with p-RSK, p(T229)-p70S6K1, and PASK antibodies. Finally, we examined the impact of PASK inhibition on S6 phosphorylation on BHD1 cell line. mTOR-pathway activity was significantly less frequent in PCNSL compared with DLBCL. p-S6 positivity was related to mTOR-pathway in DLBCL, but not in PCNSL. Among the other kinases potentially responsible for S6 phosphorylation, PASK proved to be positive in all cases of PCNSL and DLBCL. Inhibition of PASK resulted in reduced expression of p-S6 in BHD1-cells. This is the first study demonstrating an mTOR independent p-S6 activity in PCNSL and that PASK may contribute to the phosphorylation of S6. Our findings also suggest a potential role of PASK in the pathomechanism of PCNSL and in DLBCL.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Sistema Nervioso Central / Proteínas Quinasas S6 Ribosómicas / Serina-Treonina Quinasas TOR / Linfoma Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: J Neuropathol Exp Neurol Año: 2018 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias del Sistema Nervioso Central / Proteínas Quinasas S6 Ribosómicas / Serina-Treonina Quinasas TOR / Linfoma Tipo de estudio: Prognostic_studies Límite: Female / Humans / Male Idioma: En Revista: J Neuropathol Exp Neurol Año: 2018 Tipo del documento: Article País de afiliación: Hungria Pais de publicación: Reino Unido