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Schüle-Freyer, Rebecca [VerfasserIn]; Dictus, Christine [VerfasserIn]; Campos, Benito [VerfasserIn]; Wan, Feng [VerfasserIn]; Ahmadi, Rezvan [VerfasserIn]; Centner, Franz-Simon [VerfasserIn]; Grabe, Niels [VerfasserIn]; Lorenzo Bermejo, Justo [VerfasserIn]; Unterberg, Andreas [VerfasserIn]; Herold-Mende, Christel [VerfasserIn]

Potential canonical wnt pathway activation in high-grade astrocytomas

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  • Medientyp: E-Artikel
  • Titel: Potential canonical wnt pathway activation in high-grade astrocytomas
  • Beteiligte: Schüle-Freyer, Rebecca [VerfasserIn]; Dictus, Christine [VerfasserIn]; Campos, Benito [VerfasserIn]; Wan, Feng [VerfasserIn]; Ahmadi, Rezvan [VerfasserIn]; Centner, Franz-Simon [VerfasserIn]; Grabe, Niels [VerfasserIn]; Lorenzo Bermejo, Justo [VerfasserIn]; Unterberg, Andreas [VerfasserIn]; Herold-Mende, Christel [VerfasserIn]
  • Erschienen: 2 May 2012
  • Erschienen in: The ScientificWorld journal ; (2012), Artikel-ID 697313, Seite 1-11
  • Sprache: Englisch
  • DOI: 10.1100/2012/697313
  • ISSN: 1537-744X
  • Identifikator:
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: 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.
  • Zugangsstatus: Freier Zugang