FOXG1 expression shows correlation with neuronal differentiation in cerebellar development, aggressive phenotype in medulloblastomas, and survival in a xenograft model of medulloblastoma.
Hum Pathol
; 46(12): 1859-71, 2015 Dec.
Article
em En
| MEDLINE
| ID: mdl-26433703
FOXG1 is a transcription factor that interacts with multiple signaling pathways and modulates neuronal differentiation in the telencephalon. Dysregulation of FOXG1 expression has been previously reported in medulloblastoma. In this study, we demonstrate a regional specific expression of FOXG1 and its colocalization with Nestin expression in the premigratory mitotically active (outer) layer of the external granular layer of the cerebellum. An inverse expression of the granular precursor cell markers, Math1 and Musashi1, in the inner nonmitotic migratory layer of the external granular layer and in the internal granular layer was observed. Furthermore, modulation of FOXG1 in the medulloblastoma cell line, DAOY, was associated with the induction of neuronal differentiation markers and significant changes in multiple signaling pathways regulating cell proliferation, differentiation, survival, and apoptosis. Additionally, we observed enhanced survival in intracerebellar mice xenografts injected with DAOY cells bearing shFOXG1 constructs versus shLuciferase construct. Overall, these findings suggest that down-modulation of FOXG1 is a prerequisite for the onset of neuronal differentiation during cerebellar development and that a decrease of FOXG1 in medulloblastoma cells offers a survival advantage in mice. We propose that the disruption of signaling pathways that promote mature neuronal differentiation by overexpressed FOXG1 is a contributing event in the neoplastic transformation of cerebellar stem cells.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Transformação Celular Neoplásica
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Neoplasias Cerebelares
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Fatores de Transcrição Forkhead
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Células-Tronco Neurais
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Meduloblastoma
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Proteínas do Tecido Nervoso
Tipo de estudo:
Prognostic_studies
Limite:
Animals
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Humans
Idioma:
En
Revista:
Hum Pathol
Assunto da revista:
PATOLOGIA
Ano de publicação:
2015
Tipo de documento:
Article
País de publicação:
Estados Unidos