Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas

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 shor...

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Main Authors:	Schüle, Rebecca, Dictus, Christine, Campos, Benito, Wan, Feng, Felsberg, Jörg, Ahmadi, Rezvan, Centner, Franz-Simon, Grabe, Niels, Reifenberger, Guido, Bermejo, Justo L., Unterberg, Andreas, Herold-Mende, Christel
Format:	Online
Language:	English
Published:	The Scientific World Journal 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419426/

id	pubmed-3419426
recordtype	oai_dc
spelling	pubmed-34194262012-08-23 Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas Schüle, Rebecca Dictus, Christine Campos, Benito Wan, Feng Felsberg, Jörg Ahmadi, Rezvan Centner, Franz-Simon Grabe, Niels Reifenberger, Guido Bermejo, Justo L. Unterberg, Andreas Herold-Mende, Christel Research Article 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. The Scientific World Journal 2012-08-02 /pmc/articles/PMC3419426/ /pubmed/22919349 http://dx.doi.org/10.1100/2012/697313 Text en Copyright © 2012 Rebecca Schüle et al. https://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Schüle, Rebecca Dictus, Christine Campos, Benito Wan, Feng Felsberg, Jörg Ahmadi, Rezvan Centner, Franz-Simon Grabe, Niels Reifenberger, Guido Bermejo, Justo L. Unterberg, Andreas Herold-Mende, Christel
spellingShingle	Schüle, Rebecca Dictus, Christine Campos, Benito Wan, Feng Felsberg, Jörg Ahmadi, Rezvan Centner, Franz-Simon Grabe, Niels Reifenberger, Guido Bermejo, Justo L. Unterberg, Andreas Herold-Mende, Christel Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
author_facet	Schüle, Rebecca Dictus, Christine Campos, Benito Wan, Feng Felsberg, Jörg Ahmadi, Rezvan Centner, Franz-Simon Grabe, Niels Reifenberger, Guido Bermejo, Justo L. Unterberg, Andreas Herold-Mende, Christel
author_sort	Schüle, Rebecca
title	Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_short	Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_full	Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_fullStr	Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_full_unstemmed	Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_sort	potential canonical wnt pathway activation in high-grade astrocytomas
description	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.
publisher	The Scientific World Journal
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419426/
_version_	1611549788010971136

Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas

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