Characterization of chromosomal instability in murine colitis-associated colorectal cancer.

<h4>Background</h4>Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carci...

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Autores principales:	Marco Gerling, Rainer Glauben, Jens K Habermann, Anja A Kühl, Christoph Loddenkemper, Hans-Anton Lehr, Martin Zeitz, Britta Siegmund
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2011
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8f20096c9514c9090e84587efb0164f
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spelling	oai:doaj.org-article:c8f20096c9514c9090e84587efb0164f2021-11-18T06:49:39ZCharacterization of chromosomal instability in murine colitis-associated colorectal cancer.1932-620310.1371/journal.pone.0022114https://doaj.org/article/c8f20096c9514c9090e84587efb0164f2011-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/21799775/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Background</h4>Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carcinogenesis in the gut is particularly challenging. Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas. The aim of this study was to analyze mouse models of CAC with regard to CIN. Additionally, protein expression of p53, beta-catenin and Ki67 was measured to further characterize murine tumor development in comparison to UC-associated carcinogenesis in men.<h4>Methods</h4>The AOM/DSS model (n = 23) and IL-10(-/-) mice (n = 8) were applied to monitor malignancy development via endoscopy and to analyze premalignant and malignant stages of CACs. CIN was assessed using DNA-image cytometry. Protein expression of p53, beta-catenin and Ki67 was evaluated by immunohistochemistry. The degree of inflammation was analyzed by histology and paralleled to local interferon-γ release.<h4>Results</h4>CIN was detected in 81.25% of all murine CACs induced by AOM/DSS, while all carcinomas that arose in IL-10(-/-) mice were chromosomally stable. Beta-catenin expression was strongly membranous in IL-10(-/-) mice, while 87.50% of AOM/DSS-induced tumors showed cytoplasmatic and/or nuclear translocation of beta-catenin. p53 expression was high in both models and Ki67 staining revealed higher proliferation of IL-10(-/-)-induced CACs.<h4>Conclusions</h4>AOM/DSS-colitis, but not IL-10(-/-) mice, could provide a powerful murine model to mechanistically investigate CIN in colitis-associated carcinogenesis.Marco GerlingRainer GlaubenJens K HabermannAnja A KühlChristoph LoddenkemperHans-Anton LehrMartin ZeitzBritta SiegmundPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 6, Iss 7, p e22114 (2011)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Marco Gerling Rainer Glauben Jens K Habermann Anja A Kühl Christoph Loddenkemper Hans-Anton Lehr Martin Zeitz Britta Siegmund Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
description	<h4>Background</h4>Patients suffering from ulcerative colitis (UC) bear an increased risk for colorectal cancer. Due to the sparsity of colitis-associated cancer (CAC) and the long duration between UC initiation and overt carcinoma, elucidating mechanisms of inflammation-associated carcinogenesis in the gut is particularly challenging. Adequate murine models are thus highly desirable. For human CACs a high frequency of chromosomal instability (CIN) reflected by aneuploidy could be shown, exceeding that of sporadic carcinomas. The aim of this study was to analyze mouse models of CAC with regard to CIN. Additionally, protein expression of p53, beta-catenin and Ki67 was measured to further characterize murine tumor development in comparison to UC-associated carcinogenesis in men.<h4>Methods</h4>The AOM/DSS model (n = 23) and IL-10(-/-) mice (n = 8) were applied to monitor malignancy development via endoscopy and to analyze premalignant and malignant stages of CACs. CIN was assessed using DNA-image cytometry. Protein expression of p53, beta-catenin and Ki67 was evaluated by immunohistochemistry. The degree of inflammation was analyzed by histology and paralleled to local interferon-γ release.<h4>Results</h4>CIN was detected in 81.25% of all murine CACs induced by AOM/DSS, while all carcinomas that arose in IL-10(-/-) mice were chromosomally stable. Beta-catenin expression was strongly membranous in IL-10(-/-) mice, while 87.50% of AOM/DSS-induced tumors showed cytoplasmatic and/or nuclear translocation of beta-catenin. p53 expression was high in both models and Ki67 staining revealed higher proliferation of IL-10(-/-)-induced CACs.<h4>Conclusions</h4>AOM/DSS-colitis, but not IL-10(-/-) mice, could provide a powerful murine model to mechanistically investigate CIN in colitis-associated carcinogenesis.
format	article
author	Marco Gerling Rainer Glauben Jens K Habermann Anja A Kühl Christoph Loddenkemper Hans-Anton Lehr Martin Zeitz Britta Siegmund
author_facet	Marco Gerling Rainer Glauben Jens K Habermann Anja A Kühl Christoph Loddenkemper Hans-Anton Lehr Martin Zeitz Britta Siegmund
author_sort	Marco Gerling
title	Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
title_short	Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
title_full	Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
title_fullStr	Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
title_full_unstemmed	Characterization of chromosomal instability in murine colitis-associated colorectal cancer.
title_sort	characterization of chromosomal instability in murine colitis-associated colorectal cancer.
publisher	Public Library of Science (PLoS)
publishDate	2011
url	https://doaj.org/article/c8f20096c9514c9090e84587efb0164f
work_keys_str_mv	AT marcogerling characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT rainerglauben characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT jenskhabermann characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT anjaakuhl characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT christophloddenkemper characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT hansantonlehr characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT martinzeitz characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer AT brittasiegmund characterizationofchromosomalinstabilityinmurinecolitisassociatedcolorectalcancer
_version_	1718424379166031872

Characterization of chromosomal instability in murine colitis-associated colorectal cancer.

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