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: | , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2 May 2012
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| In: |
The ScientificWorld journal
Year: 2012, Pages: 1-11 |
| ISSN: | 1537-744X |
| DOI: | 10.1100/2012/697313 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1100/2012/697313 Verlag, kostenfrei, Volltext: https://onlinelibrary.wiley.com/doi/full/10.1100/2012/697313 
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| Author Notes: | 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 |
| Summary: | 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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| Item Description: | Gesehen am 13.04.2018 |
| Physical Description: | Online Resource |
| ISSN: | 1537-744X |
| DOI: | 10.1100/2012/697313 |