Niggli
Fakultäten » Medizinische Fakultät » Kinderspital Zürich: Medizinische Klinik » Onkologie, Abteilung » Prof. Dr. Felix Niggli » Niggli
Completed research project
| Title / Titel | Generation of a Wilms tumor mouse model: role of wnt signaling | ||||||
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| Abstract (PDF, 14 KB) | |||||||
| Summary / Zusammenfassung | Wilms’ tumor, a malignant disease of the embryonal kidney, is thought to arise from the pluripotent blastemal cells present in the induced metanephric mesenchyme during early kidney development. For tumorigenesis to occur, activation of the proto-oncogene â-catenin as well as inactivation of the WT1 tumor suppressor protein are known to play crucial roles. In this project we would therefore like to investigate the molecular mechanisms mediated by these proteins in more detail by establishing the first transgenic Wilms’ tumor model. This will be achieved through introduction of â -catenin carrying a known activating mutation into the germline of mice. To achieve selective expression of the mutated â-catenin in the developing kidney, we will use the highly specific murine Pax8 promoter which will be integrated at the same time into the tetracycline dependent expression system to allow for reversible expression. In addition, a complementary cell culture system will be established to study wnt signalling in embryonic kidney cells. The establishment of a transgenic Wilms’ tumor model will allow to address a number of questions regarding the biology of this tumor. -Is a mutated â -catenin responsible for tumor initiation or progression? -Is inactivation of the WT1 tumor suppressor responsible for tumor initiation or progression and how do the two genes cooperate? -Which target genes are activated by mutated â-catenin in embryonic kidney cells? |
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| Publications / Publikationen | Koesters R., Ruediger R., Kopp-Schneider A., Betts D., Adams V., Niggli F., Briner J., vonKnebel Doeberitz M. (1999). Mutational activation of the â-Catenin proto-oncogen is a common event in the development of Wilms‘ tumors. Cancer Res 59(16): 3880-3882.Koesters R., Niggli F., von Knebel Doeberitz M, Stallmach T. (2003) Nuclear Accumulation of ß-Catenin Protein in Wilms’ Tumors. J Pathol; 199; 68-76. | ||||||
| Keywords / Suchbegriffe | transgenic mice, wnt signalling, b-catenin, gene expression profiling, nephroblastoma | ||||||
| Project leadership and contacts / Projektleitung und Kontakte |
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| Funding source(s) / Unterstützt durch |
SNF (Personen- und Projektförderung) |
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| In collaboration with / In Zusammenarbeit mit |
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| Duration of Project / Projektdauer | Jan 2004 to Dec 2006 |