Temporal blastemal cell gene expression analysis in the kidney reveals new Wnt and related signaling pathway genes to be essential for Wilms' tumor onset

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Citações na Scopus
23
Tipo de produção
article
Data de publicação
2011
Título da Revista
ISSN da Revista
Título do Volume
Editora
NATURE PUBLISHING GROUP
Autores
MASCHIETTO, M.
PICCOLI, F. S.
RICCA, T. I.
DIAS, A. A. M.
COUDRY, R. A.
GALANTE, P. A.
TORRES, C.
FAHHAN, L.
LOURENCO, S.
Citação
CELL DEATH & DISEASE, v.2, article ID e224, 12p, 2011
Projetos de Pesquisa
Unidades Organizacionais
Fascículo
Resumo
Wilms' tumors (WTs) originate from metanephric blastema cells that are unable to complete differentiation, resulting in triphasic tumors composed of epithelial, stromal and blastemal cells, with the latter harboring molecular characteristics similar to those of the earliest kidney development stages. Precise regulation of Wnt and related signaling pathways has been shown to be crucial for correct kidney differentiation. In this study, the gene expression profile of Wnt and related pathways was assessed in laser-microdissected blastemal cells in WTs and differentiated kidneys, in human and in four temporal kidney differentiation stages (i.e. E15.5, E17.5, P1.5 and P7.5) in mice, using an orthologous cDNA microarray platform. A signaling pathway-based gene signature was shared between cells of WT and of earliest kidney differentiation stages, revealing genes involved in the interruption of blastemal cell differentiation in WT. Reverse transcription-quantitative PCR showed high robustness of the microarray data demonstrating 75 and 56% agreement in the initial and independent sample sets, respectively. The protein expression of CRABP2, IGF2, GRK7, TESK1, HDGF, WNT5B, FZD2 and TIMP3 was characterized in WTs and in a panel of human fetal kidneys displaying remarkable aspects of differentiation, which was recapitulated in the tumor. Taken together, this study reveals new genes candidate for triggering WT onset and for therapeutic treatment targets. Cell Death and Disease (2011) 2, e224; doi:10.1038/cddis.2011.105; published online 3 November 2011
Palavras-chave
Wilms' tumor, blastemal component, Wnt signaling pathway, kidney development, gene expression
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