Myogenesis in Wilms' tumors is associated with mutations of the WT1 gene and activation of Bcl-2 and the Wnt signaling pathway.
Pediatr Dev Pathol
; 7(2): 125-37, 2004.
Article
em En
| MEDLINE
| ID: mdl-14994125
ABSTRACT
Wilms tumors with WT1 mutations [ WT1(-)] have a stromal-predominant histology with varying extents of rhabdomyogenesis. These tumors also frequently have mutations in the beta-catenin gene ( CTNNB1). We have investigated the molecular events that may explain the origins of rhabdomyogenesis in WT1(-) tumors. Of 35 Wilms tumors, we identified 12 with WT1 mutations, of which 9 carried CTNNB1 mutations. We compared WT1 wild-type tumors [ WT1(+)] with WT1(-) tumors for histological features, localization of beta-catenin, Bcl-2 expression, and apoptosis using an in-situ end-labeling technique. WT1(+) tumors showed triphasic and blastemal- and epithelial predominant-histology. Expression of WT1, beta-catenin, and Bcl-2 recapitulated those of normal kidney epithelial development. Localization of beta-catenin was observed in the cytoplasm and cytoplasmic membrane of early glomerular epithelial structures. Bcl-2 is also expressed in condensing blastema and early glomerular epithelial structures which had little apoptosis. WT1(-) tumors, regardless of whether CTNNB1 mutations were detected or not, showed a stromal-rich phenotype with abundant expression of beta-catenin in the nucleus of the rhabdomyoblasts. Bcl-2 was expressed in rhabdomyoblasts, but not in blastemal cells undergoing apoptosis, suggesting that WT1 regulates Bcl-2 positively in the epithelial pathway, but negatively in the myogenic pathway. These data indicate that mutations in WT1 might alter the Wnt signaling pathway and Bcl-2 related-apoptosis. In WT1(-) tumors, the nuclear accumulation of beta-catenin and Bcl-2 expression are associated with rhabdomyogenesis, and dysregulation of Bcl-2 may be a mechanism by which the histogenesis (loss of blastemal component, muscle differentiation) may be explained.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Genes do Tumor de Wilms
/
Proteínas Proto-Oncogênicas
/
Tumor de Wilms
/
Proteínas Proto-Oncogênicas c-bcl-2
/
Desenvolvimento Muscular
/
Neoplasias Renais
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Pediatr Dev Pathol
Assunto da revista:
PATOLOGIA
/
PEDIATRIA
Ano de publicação:
2004
Tipo de documento:
Article
País de afiliação:
Nova Zelândia