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Senanayake, U; Koller, K; Pichler, M; Leuschner, I; Strohmaier, H; Hadler, U; Das, S; Hoefler, G; Guertl, B.
The pluripotent renal stem cell regulator SIX2 is activated in renal neoplasms and influences cellular proliferation and migration.
Hum Pathol. 2013; 44(3):336-345 Doi: 10.1016/j.humpath.2012.05.021
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Führende Autor*innen der Med Uni Graz
Gürtl-Lackner Barbara
Senanayake Upeka
Co-Autor*innen der Med Uni Graz
Das Suman Kumar
Höfler Gerald
Koller Karin
Pichler Martin
Strohmaier Heimo

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Embryonal renal mesenchyme contains pluripotent progenitor cells characterized by expression of SIX2, which suppresses cellular differentiation. Additionally hypomethylation of the promotor region in renal neoplasms indicates a role of SIX2 in tumorigenesis. This study focuses therefore on the investigation of SIX2 in different renal neoplasms and the mode and consequences of SIX2 activation. Expression of SIX2 was determined in renal cell carcinomas, nephroblastomas, and dysplastic kidneys using immunohistochemistry and quantitative real-time polymerase chain reaction. Its potential mode of activation was assessed by measuring upstream activators by quantitative real-time polymerase chain reaction and the level of methylation of the promoter region by quantitative DNA methylation analysis. Consequences of SIX2 activation were investigated by overexpressing SIX2 in a cell line. Forty-seven of 49 renal clear cell carcinomas showed nuclear staining of SIX2, whereas all papillary carcinomas were negative. In nephroblastomas of various subtypes blastema showed a significant up-regulation (P < .01) and a strong nuclear protein expression of SIX2 in contrast to negative epithelial and mesenchymal areas. 11 cases of dysplastic kidneys were entirely negative. Upstream activators of SIX2 indicated an activation of the signal transduction pathway in most samples. No difference of promoter methylation status was observed between blastema and epithelial structures. A significantly higher percentage of cells in the S-phase and an increased migration were detected in the cell-line overexpressing SIX2. Our study suggests that activation of SIX2 might contribute to the pathogenesis of renal clear cell carcinomas and nephroblastomas. SIX2 also appears to be a valuable marker for minimal residual blastema contributing to the prognosis of nephroblastomas.
Find related publications in this database (using NLM MeSH Indexing)
Carcinoma, Renal Cell - genetics Carcinoma, Renal Cell - metabolism Carcinoma, Renal Cell - pathology
Cell Differentiation -
Cell Line, Tumor -
Cell Movement -
Cell Proliferation -
Child -
DNA Methylation -
Gene Expression Regulation, Neoplastic -
Homeodomain Proteins - genetics Homeodomain Proteins - metabolism
Humans -
Immunohistochemistry -
Kidney Neoplasms - genetics Kidney Neoplasms - metabolism Kidney Neoplasms - pathology
Multicystic Dysplastic Kidney - genetics Multicystic Dysplastic Kidney - metabolism Multicystic Dysplastic Kidney - pathology
Nerve Tissue Proteins - genetics Nerve Tissue Proteins - metabolism
Nuclear Proteins - genetics Nuclear Proteins - metabolism
Phenotype -
Pluripotent Stem Cells - metabolism Pluripotent Stem Cells - pathology
Prognosis -
Promoter Regions, Genetic - genetics
Real-Time Polymerase Chain Reaction -
Signal Transduction -
Tumor Markers, Biological - genetics Tumor Markers, Biological - metabolism
Up-Regulation -
Wilms Tumor - genetics Wilms Tumor - metabolism Wilms Tumor - pathology

Find related publications in this database (Keywords)
Renal cell carcinoma
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