Nuclear accumulation of beta-catenin protein indicates frequent activation of Wnt-signaling in chemically-induced rat nephroblastomas

Ehrlich, David and Bruder, Elisabeth and Thome, Martin and Gutt, Carsten and von Knebel Doeberitz, Magnus and Niggli, Felix and Perantoni, Alan and Bode, Manja and Koesters, Robert. (2009) Nuclear accumulation of beta-catenin protein indicates frequent activation of Wnt-signaling in chemically-induced rat nephroblastomas. Pediatric and developmental pathology : official journal of the Society for Pediatric Pathology, Vol. 6. p. 1.

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Official URL: http://edoc.unibas.ch/dok/A6008045

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Aberrant wnt-signaling caused by mutations in CTNNB1 occurs in about 15% of Wilms tumors. Nuclear beta-catenin protein, a substitute marker of active wnt-signaling, has been detected in an even higher proportion (<50%) of Wilms tumors suggesting alternative genetic pathways leading to beta-catenin activation. Thus, targeting wnt-signaling may become an important future therapeutic strategy in Wilms tumor patients. Currently, chemically-induced rat nephroblastomas provide the only available rodent model for this tumor. To determine the contribution of active wnt-signaling in this model, we investigated 25 chemically-induced rat nephroblastomas for beta-catenin protein expression and for Ctnnb1 exon 3 mutations. Using immunohistochemistry 16 of 25 tumors showed strong nuclear accumulation of beta-catenin protein although in a heterogenous pattern. Blastemal and mesenchymal compartments displayed nuclear positive cells more frequently than areas of epithelial differentiation. Interestingly, we found no mutation of exon 3 of Ctnnb1 in any of the 25 tumors analysed. In conclusion, our findings suggest activation of wnt-signaling in the vast majority of chemically-induced rat nephroblastomas. Nuclear expression of beta-catenin in the absence of Ctnnb1 mutations implies, however, alternate mutational targets in rat nephroblastomas. Chemically-induced rat nephroblastomas may constitute a suitable model system to test future anti-cancer drugs targeting the wnt-signaling pathway. betabeta.
Faculties and Departments:03 Faculty of Medicine > Bereich Querschnittsfächer (Klinik) > Pathologie USB
03 Faculty of Medicine > Departement Klinische Forschung > Bereich Querschnittsfächer (Klinik) > Pathologie USB
UniBasel Contributors:Bruder, Elisabeth
Item Type:Article, refereed
Article Subtype:Research Article
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:01 Feb 2013 08:46
Deposited On:01 Feb 2013 08:40

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