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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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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Scientific World Journal 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419426/
https://www.ncbi.nlm.nih.gov/pubmed/22919349
http://dx.doi.org/10.1100/2012/697313
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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
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
collection PubMed
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.
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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 ScientificWorldJournal 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.
spellingShingle Research Article
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
title 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_short Potential Canonical Wnt Pathway Activation in High-Grade Astrocytomas
title_sort potential canonical wnt pathway activation in high-grade astrocytomas
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3419426/
https://www.ncbi.nlm.nih.gov/pubmed/22919349
http://dx.doi.org/10.1100/2012/697313
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