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

Autor(es):Mostrar menos -

Maschietto, Mariana ^[1] ; de Camargo, Beatriz ^[2] ; Brentani, Helena ^[3] ; Grundy, Paul ^[4] ; Sredni, Simone T. ^[5] ; Torres, Cesar ^[3] ; Mota, Louise D. ^[1] ; Cunha, Isabela W. ^[6] ; Patrao, Diogo F. C. ^[3] ; Costa, Cecilia M. L. ^[2] ; Soares, Fernando A. ^[6] ; Brentani, Ricardo R. ^[7] ; Carraro, Dirce M. ^[1]

Afiliação do(s) autor(es)

^[1] Hosp AC Camargo Fund Antonio Prudente, Lab Genom & Mol Biol, BR-01509010 Sao Paulo - Brazil

^[2] Hosp AC Camargo Fund Antonio Prudente, Dept Pediat, BR-01509010 Sao Paulo - Brazil

^[3] Hosp AC Camargo Fund Antonio Prudente, Lab Bioinformat, BR-01509010 Sao Paulo - Brazil

^[4] Univ Alberta, Dept Pediat & Oncol, Edmonton, AB - Canada

^[5] Northwestern Univ, Feinberg Sch Med, Childrens Mem Res Ctr, Chicago, IL 60611 - USA

^[6] Hosp AC Camargo Fund Antonio Prudente, Dept Anat Pathol, BR-01509010 Sao Paulo - Brazil

^[7] Univ Sao Paulo, Fac Med, Dept Oncol, BR-09500900 Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: ONCOLOGY; v. 75, n. 1-2, p. 81-91, 2008.
• Citações Web of Science: 16

Resumo

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. (AU)

• Processo FAPESP: 98/14335-2 - Antonio Prudente Cancer Research Center
• Beneficiário: Fernando Augusto Soares
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• 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
• Processo FAPESP: 06/00081-7 - Caracterizacao da expressao dos genes da via de sinalizacao wnt e do processo de transicao epitelio-mesenquima durante a embriogenese de rim e figado e suas implicacoes em tumores embrionarios.
• Beneficiário: Mariana Camargo Maschietto
• Modalidade de apoio: Bolsas no Brasil - Doutorado