Abstract | BACKGROUND: METHODS: 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. RESULTS: 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. CONCLUSIONS: AOM/DSS- colitis, but not IL-10(-/-) mice, could provide a powerful murine model to mechanistically investigate CIN in colitis-associated carcinogenesis.
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Authors | Marco Gerling, Rainer Glauben, Jens K Habermann, Anja A Kühl, Christoph Loddenkemper, Hans-Anton Lehr, Martin Zeitz, Britta Siegmund |
Journal | PloS one
(PLoS One)
Vol. 6
Issue 7
Pg. e22114
( 2011)
ISSN: 1932-6203 [Electronic] United States |
PMID | 21799775
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Ki-67 Antigen
- Tumor Suppressor Protein p53
- beta Catenin
- Interleukin-10
- Interferon-gamma
- Dextran Sulfate
- Azoxymethane
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Topics |
- Animals
- Azoxymethane
(adverse effects)
- Cell Proliferation
- Chromosomal Instability
- Colitis
(complications)
- Colorectal Neoplasms
(complications, genetics, metabolism, pathology)
- Dextran Sulfate
(adverse effects)
- Endoscopy, Digestive System
- Gene Expression Regulation, Neoplastic
- Humans
- Interferon-gamma
(metabolism)
- Interleukin-10
(deficiency)
- Ki-67 Antigen
(metabolism)
- Mice
- Neoplasm Staging
- Tumor Suppressor Protein p53
(metabolism)
- beta Catenin
(metabolism)
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