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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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Autor(es):
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Maschietto, M. [1] ; Trape, A. P. [2, 1] ; Piccoli, F. S. [1] ; Ricca, T. I. [1] ; Dias, A. A. M. [3] ; Coudry, R. A. [4] ; Galante, P. A. [5] ; Torres, C. [6] ; Fahhan, L. [7] ; Lourenco, S. [4] ; Grundy, P. E. [8] ; de Camargo, B. [9] ; de Souza, S. [5] ; Neves, E. J. [7] ; Soares, F. A. [4] ; Brentani, H. [10] ; Carraro, D. M. [1]
Número total de Autores: 17
Afiliação do(s) autor(es):
[1] CIPE Hosp AC Camargo, Lab Genom & Mol Biol, BR-01509010 Sao Paulo - Brazil
[2] Univ Sao Paulo, Fac Med, Dept Radiol & Oncol, Sao Paulo - Brazil
[3] Univ Fed Minas Gerais, Lab Expt Genet, Dept Gen Biol, Belo Horizonte, MG - Brazil
[4] AC Camargo Hosp, Dept Anat Pathol, Sao Paulo - Brazil
[5] Ludwig Inst Canc Res, Lab Bioinformat, Sao Paulo - Brazil
[6] CIPE Hosp AC Camargo, Lab Bioinformat, BR-01509010 Sao Paulo - Brazil
[7] Univ Sao Paulo, Inst Matemat & Estat, Sao Paulo - Brazil
[8] Pediat Hematol Oncol & Palliat Care Stollery Chil, Edmonton, AB - Canada
[9] Inst Nacl Canc, Res Pediat Hematol Oncol Program, Rio De Janeiro - Brazil
[10] Univ Sao Paulo, Fac Med, Dept Psiquiatria, Sao Paulo - Brazil
Número total de Afiliações: 10
Tipo de documento: Artigo Científico
Fonte: CELL DEATH & DISEASE; v. 2, NOV 2011.
Citações Web of Science: 17
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 (AU)

Processo FAPESP: 10/00223-1 - Genes de vias de sinalização envolvidos na recapitulação da nefrogênese pelo tumor de Wilms: definição do espectro de mutações e caracterização dos aspectos regulatórios e funcionais
Beneficiário:Dirce Maria Carraro
Modalidade de apoio: Auxílio à Pesquisa - Regular
Processo FAPESP: 06/00054-0 - Análise de expressão gênica de vários estágios de desenvolvimento do rim e fígado e suas implicações em tumores embrionários
Beneficiário:Dirce Maria Carraro
Modalidade de apoio: Auxílio à Pesquisa - Regular