gms | German Medical Science

81. Jahresversammlung der Deutschen Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

Deutsche Gesellschaft für Hals-Nasen-Ohren-Heilkunde, Kopf- und Hals-Chirurgie e. V.

12.05. - 16.05.2010, Wiesbaden

Increased transcript levels of the WNT-pathway genes β-catenin, GSK3β, APC and Axin2 in juvenile angiofibromas

Meeting Abstract

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  • author presenting/speaker Stefanie Weber - Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Vivienne Willnecker - Universitätskliniken des Saarlandes, Homburg/Saar, Germany
  • Olaf Wendler - Universitätskliniken Erlangen, Germany
  • corresponding author Bernhard Schick - Universitätskliniken des Saarlandes, Homburg/Saar, Germany

German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. 81st Annual Meeting of the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery. Wiesbaden, 12.-16.05.2010. Düsseldorf: German Medical Science GMS Publishing House; 2010. Doc10hno018

DOI: 10.3205/10hno018, URN: urn:nbn:de:0183-10hno0184

Veröffentlicht: 6. Juli 2010

© 2010 Weber et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

Introduction: Juvenile angiofibroma is a rare fibro-vascular, mostly aggressive growing tumor occurring almost exclusively in adolescent males. In addition to the frequent finding of β-catenin mutations at the GSK3β phosphorylation site in 75% of analyzed juvenile angiofibromas, a strong nuclear accumulation of β-catenin protein was proven (Abraham et al. 2001, Zhang et al. 2003, Rippel et al. 2003). GSK3β is a regulator, which marks β-catenin for its degradation through phosphorylation. Loss of β-catenin phosphorylation due to the detected mutations is suggested to be the reason for the increased β-catenin protein levels.

The aim of this study was the first quantitative analysis of β-catenin transcripts and other WNT-pathway members as well as to search for β-catenin mutations.

Methods: RNA was isolated from 5 tumors and 2 normal control tissues (inferior turbinates) and transcribed into cDNA. Expression of the WNT-pathway genes β-catenin, GSK3β, APC, Axin1 and Axin2 was measured by quantitative Realtime-PCR. The cDNA was further analyzed by direct sequencing to determine whether any mutations for the GSK3β binding site exist.

Results: β-catenin point mutations were detected in four out of five tumors. These mutations lead to an exchange of the serine residues phosphorylated by GSK3β or an amino acid in its close proximity. In addition clear differences between the patterns of expression of the examined transcripts were observed. Four out of five tumors showed in part a substantial increase in transcripts of β-catenin, GSK3β, APC and Axin2 in comparison to normal tissue.

Conclusion: Our analysis confirmed the observation of frequent β-catenin mutations in juvenile angiofibromas. However, the finding of increased transcript levels of the WNT-pathway members might suggest additional factors, next to the loss of phosphorylation, responsible for the increased levels of β-catenin protein in juvenile angiofibromas.