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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

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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Author(s):
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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]
Total Authors: 17
Affiliation:
[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
Total Affiliations: 10
Document type: Journal article
Source: CELL DEATH & DISEASE; v. 2, NOV 2011.
Web of Science Citations: 17
Abstract

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)

FAPESP's process: 10/00223-1 - Genes of signaling pathways involved in the recapitulation of nephrogenesis by Wilms tumor: definition of the mutation spectrum and characterization of regulatory and functional aspects
Grantee:Dirce Maria Carraro
Support Opportunities: Regular Research Grants
FAPESP's process: 06/00054-0 - Gene expression analysis of kidney and liver development stages and their implications in embryonic tumors
Grantee:Dirce Maria Carraro
Support Opportunities: Regular Research Grants