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In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence

BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands...

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Autores principales: Götzel, Katharina, Chemnitzer, Olga, Maurer, Luisa, Dietrich, Arne, Eichfeld, Uwe, Lyros, Orestis, Moulla, Yusef, Niebisch, Stefan, Mehdorn, Matthias, Jansen-Winkeln, Boris, Vieth, Michael, Hoffmeister, Albrecht, Gockel, Ines, Thieme, René
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404335/
https://www.ncbi.nlm.nih.gov/pubmed/30841855
http://dx.doi.org/10.1186/s12876-019-0957-5
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author Götzel, Katharina
Chemnitzer, Olga
Maurer, Luisa
Dietrich, Arne
Eichfeld, Uwe
Lyros, Orestis
Moulla, Yusef
Niebisch, Stefan
Mehdorn, Matthias
Jansen-Winkeln, Boris
Vieth, Michael
Hoffmeister, Albrecht
Gockel, Ines
Thieme, René
author_facet Götzel, Katharina
Chemnitzer, Olga
Maurer, Luisa
Dietrich, Arne
Eichfeld, Uwe
Lyros, Orestis
Moulla, Yusef
Niebisch, Stefan
Mehdorn, Matthias
Jansen-Winkeln, Boris
Vieth, Michael
Hoffmeister, Albrecht
Gockel, Ines
Thieme, René
author_sort Götzel, Katharina
collection PubMed
description BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3β was performed in an in vitro cell culture model of Barrett’s esophagus. Representing the Barrett’s sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. RESULTS: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett’s metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1–10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. CONCLUSION: Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett’s esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett’s progression and the underlying pathological mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-019-0957-5) contains supplementary material, which is available to authorized users.
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spelling pubmed-64043352019-03-18 In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence Götzel, Katharina Chemnitzer, Olga Maurer, Luisa Dietrich, Arne Eichfeld, Uwe Lyros, Orestis Moulla, Yusef Niebisch, Stefan Mehdorn, Matthias Jansen-Winkeln, Boris Vieth, Michael Hoffmeister, Albrecht Gockel, Ines Thieme, René BMC Gastroenterol Research Article BACKGROUND: An altered Wnt-signaling activation has been reported during Barrett’s esophagus progression, but with rarely detected mutations in APC and β-catenin (CTNNB1) genes. METHODS: In this study, a robust in-depth expression pattern analysis of frizzled receptors, co-receptors, the Wnt-ligands Wnt3a and Wnt5a, the Wnt-signaling downstream targets Axin2, and CyclinD1, as well as the activation of the intracellular signaling kinases Akt and GSK3β was performed in an in vitro cell culture model of Barrett’s esophagus. Representing the Barrett’s sequence, we used normal esophageal squamous epithelium (EPC-1, EPC-2), metaplasia (CP-A) and dysplasia (CP-B) to esophageal adenocarcinoma (EAC) cell lines (OE33, OE19) and primary specimens of squamous epithelium, metaplasia and EAC. RESULTS: A loss of Wnt3a expression was observed beginning from the metaplastic cell line CP-A towards dysplasia (CP-B) and EAC (OE33 and OE19), confirmed by a lower staining index of WNT3A in Barrett’s metaplasia and EAC, than in squamous epithelium specimens. Frizzled 1–10 expression analysis revealed a distinct expression pattern, showing the highest expression for Fzd2, Fzd3, Fzd4, Fzd5, Fzd7, and the co-receptor LRP5/6 in EAC cells, while Fzd3 and Fzd7 were rarely expressed in primary specimens from squamous epithelium. CONCLUSION: Despite the absence of an in-depth characterization of Wnt-signaling-associated receptors in Barrett’s esophagus, by showing variations of the Fzd- and co-receptor profiles, we provide evidence to have a significant role during Barrett’s progression and the underlying pathological mechanisms. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-019-0957-5) contains supplementary material, which is available to authorized users. BioMed Central 2019-03-06 /pmc/articles/PMC6404335/ /pubmed/30841855 http://dx.doi.org/10.1186/s12876-019-0957-5 Text en © The Author(s). 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research Article
Götzel, Katharina
Chemnitzer, Olga
Maurer, Luisa
Dietrich, Arne
Eichfeld, Uwe
Lyros, Orestis
Moulla, Yusef
Niebisch, Stefan
Mehdorn, Matthias
Jansen-Winkeln, Boris
Vieth, Michael
Hoffmeister, Albrecht
Gockel, Ines
Thieme, René
In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title_full In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title_fullStr In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title_full_unstemmed In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title_short In-depth characterization of the Wnt-signaling/β-catenin pathway in an in vitro model of Barrett’s sequence
title_sort in-depth characterization of the wnt-signaling/β-catenin pathway in an in vitro model of barrett’s sequence
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6404335/
https://www.ncbi.nlm.nih.gov/pubmed/30841855
http://dx.doi.org/10.1186/s12876-019-0957-5
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