Potential canonical wnt pathway activation in high-grade astrocytomas

• Verfasst von: Schüle-Freyer, Rebecca [VerfasserIn]
• Verfasst von: Dictus, Christine [VerfasserIn]
• Verfasst von: Campos, Benito [VerfasserIn]
• Verfasst von: Wan, Feng [VerfasserIn]
• Verfasst von: Ahmadi, Rezvan [VerfasserIn]
• Verfasst von: Centner, Franz-Simon [VerfasserIn]
• Verfasst von: Grabe, Niels [VerfasserIn]
• Verfasst von: Lorenzo Bermejo, Justo [VerfasserIn]
• Verfasst von: Unterberg, Andreas [VerfasserIn]
• Verfasst von: Herold-Mende, Christel [VerfasserIn]
• Titel: Potential canonical wnt pathway activation in high-grade astrocytomas
• Verf.angabe: Rebecca Schüle, Christine Dictus, Benito Campos, Feng Wan, Jörg Felsberg, Rezvan Ahmadi, Franz-Simon Centner, Niels Grabe, Guido Reifenberger, Justo L. Bermejo, Andreas Unterberg, and Christel Herold-Mende
• E-Jahr: 2012
• Jahr: 2 May 2012
• Umfang: 11 S.
• Fussnoten: Gesehen am 13.04.2018
• Titel Quelle: Enthalten in: The ScientificWorld journal
• Ort Quelle: Boynton Beach, Fla. : [Verlag nicht ermittelbar], 2000
• Jahr Quelle: 2012
• Band/Heft Quelle: (2012), Artikel-ID 697313, Seite 1-11
• ISSN Quelle: 1537-744X
• DOI: doi:10.1100/2012/697313
• Datenträger: Online-Ressource
• Sprache: eng
• K10plus-PPN: 1572008547

Abstract

Aberrant wnt pathway activation through cytoplasmic stabilization of β-catenin is crucial for the development of various human malignancies. In gliomagenesis, the role of canonical (i.e., β-catenin-dependent) signalling is largely unknown. Here, we studied canonical wnt pathway activation in 15 short-term cultures from high-grade gliomas and potential pathomechanisms leading to cytoplasmic β-catenin accumulation. Furthermore, we assessed the prognostic relevance of β-catenin expression in a tissue microarray comprising 283 astrocytomas. Expression of β-catenin, its transcriptional cofactors TCF-1 and TCF-4 as well as GSK-3β and APC, constituents of the β-catenin degradation complex was confirmed by RT-PCR in all cultures. A cytoplasmic β-catenin pool was detectable in 13/15 cultures leading to some transcriptional activity assessed by luciferase reporter gene assay in 8/13. Unlike other malignancies, characteristic mutations of β-catenin and APC leading to cytoplasmic stabilization of β-catenin were excluded by direct sequencing or protein truncation test. In patient tissues, β-catenin expression was directly and its degradation product's (β-catenin-P654) expression was inversely correlated with WHO grade. Increased β-catenin expression and low β-catenin-P654 expression were associated with shorter survival. Altogether, we report on potential canonical wnt pathway activation in high-grade gliomas and demonstrate that β-catenin expression in astrocytomas is associated with increased malignancy and adverse outcome.