Molecular profiling of isolated histological components of Wilms tumor implicates a common role for the Wnt signaling pathway in kidney and tumor development

Molecular profiling of isolated histological components of Wilms tumor implicates a common role for the Wnt signaling pathway in kidney and tumor development

Author Maschietto, Mariana Google Scholar
Camargo, Beatriz de Google Scholar
Brentani, Helena Google Scholar
Grundy, Paul Google Scholar
Sredni, Simone T. Google Scholar
Torres, Cesar Google Scholar
Mota, Louise D. Google Scholar
Cunha, Isabela W. Google Scholar
Patrao, Diogo F. C. Google Scholar
Costa, Cecilia M. L. Google Scholar
Soares, Fernando A. Google Scholar
Brentani, Ricardo R. Google Scholar
Carraro, Dirce M. Google Scholar
Institution Hosp AC Camargo Fund Antonio Prudente
Universidade Federal de São Paulo (UNIFESP)
Universidade de São Paulo (USP)
Univ Alberta
Northwestern Univ
Abstract Wilms tumor (WT), a tumor composed of three histological components - blastema (BL), epithelia and stroma - is considered an appropriate model system to study the biological relationship between differentiation and tumorigenesis. To investigate molecular associations between nephrogenesis and WT, the gene expression pattern of individual cellular components was analyzed, using a customized platform containing 4,608 genes. WT gene expression patterns were compared to genes regulated during kidney differentiation. BL had a closer gene expression pattern to the earliest stage of normal renal development. the BL gene expression pattern was compared to that of fetal kidney (FK) and also between FK and mature kidney, identifying 25 common de-regulated genes supposedly involved in the earliest events of WT onset. Quantitative RT-PCR was performed, confirming the difference in expression levels for 13 of 16 genes (81.2%) in the initial set and 8 of 13 (61.5%) in an independent set of samples. An overrepresentation of genes belonging to the Wnt signaling pathway was identified, namely PLCG2, ROCK2 and adenomatous polyposis coli (APC). Activation of the Wnt pathway was confirmed in WT, using APC at protein level and PLCG2 at mRNA and protein level. APC showed positive nuclear immunostaining for an independent set of WT samples, similarly to the FK in week 11. Lack of PLCG2 expression was confirmed in WT and in FK until week 18. Taken together, these results provided molecular evidence of the recapitulation of the embryonic kidney by WT as well as involvement of the Wnt pathway in the earliest events of WT onset. Copyright (C) 2008 S. Karger AG, Basel.
Keywords blastemal component
gene expression analysis
kidney development
Wilms tumor
Wnt signaling pathway
Language English
Sponsor Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Grant number FAPESP: 98/14335-2
FAPESP: 06/00054-0
FAPESP: 06/00081-7
Date 2008-01-01
Published in Oncology. Basel: Karger, v. 75, n. 1-2, p. 81-91, 2008.
ISSN 0030-2414 (Sherpa/Romeo, impact factor)
Publisher Karger
Extent 81-91
Origin http://dx.doi.org/10.1159/000155210
Access rights Closed access
Type Article
Web of Science ID WOS:000259892700011
URI http://repositorio.unifesp.br/handle/11600/30359

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