| Autor: |
Kensuke Tateishi, Naoki Ikegaya, Naoko Udaka, Jo Sasame, Takahiro Hayashi, Yohei Miyake, Tetsuhiko Okabe, Ryogo Minamimoto, Hidetoshi Murata, Daisuke Utsunomiya, Shoji Yamanaka, Tetsuya Yamamoto |
| Jazyk: |
angličtina |
| Rok vydání: |
2020 |
| Předmět: |
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| Zdroj: |
Acta Neuropathologica Communications, Vol 8, Iss 1, Pp 1-8 (2020) |
| Druh dokumentu: |
article |
| ISSN: |
2051-5960 |
| DOI: |
10.1186/s40478-020-01023-3 |
| Popis: |
Abstract We present a case of a 14-year old boy with tumor-associated refractory epilepsy. Positron emission tomography imaging demonstrated a region with heterogeneous high 11C-methionine uptake and a region with homogenous low 18F-fluorodeoxyglucose uptake within the tumor. Histopathological and genomic analyses confirmed the tumor as BRAF V600E-mutated polymorphous low-grade neuroepithelial tumor of the young (PLNTY). Within the high-methionine-uptake region, we observed increased protein levels of L-type amino acid transporter 1 (LAT1), a major transporter of methionine; c-Myc; and constituents of the mitogen-activated protein kinase (MAPK) pathway. We also found that LAT1 expression was linked to the BRAF V600E mutation and subsequent activation of MAPK signaling and c-Myc. Pharmacological and genetic inhibition of the MAPK pathway suppressed c-Myc and LAT1 expression in BRAF V600E-mutated PLNTY and glioblastoma cells. The BRAF inhibitor dabrafenib moderately suppressed cell viability in PLNTY. Collectively, our results indicate that BRAF V600E mutation-activated MAPK signaling and downstream c-Myc induces specific metabolic alterations in PLNTY, and may represent an attractive target in the treatment of the disease. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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