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Tumor formation in a mouse model of colitis associated colon cancer does not require COX-1 or COX-2 expression

kevinlin2009 添加于 2010-3-3 17:05 | 2942 次阅读 | 0 个评论

作者
Ishikawa TO, Herschman HR
摘要
Cyclooxygenase-2 (Cox-2), a key enzyme of prostanoid biosynthesis, plays an important role in both hereditary and spontaneous colon cancer. Individuals with ulcerative colitis are also at high risk for colorectal cancer. To investigate the role of Cox-2 in colitis-associated colon cancer, we subjected Cox-2 luciferase knock-in mice and Cox-2 knockout mice to a well known mouse model of colitis-associated cancer in which animals are treated with a single azoxymethane (AOM) injection followed by dextran sulfate sodium (DSS) administration. Tumors induced by AOM and DSS expressed significantly higher Cox-2 levels when compared with surrounding areas of colon, as detected both by luciferase reporter gene expression driven from the endogenous Cox-2 promoter and by Western blotting of COX-2 protein in Cox-2 luciferase heterozygous knock-in mice. Immunofluorescence revealed that tumor stromal fibroblasts, macrophages and endothelial cells express COX-2 protein. In contrast, little COX-2 expression was observed in myofibroblasts or epithelial cells. Despite a significant elevation of COX-2 expression in AOM/DSS induced colon tumors in wild-type mice, similar tumors developed in AOM/DSS treated Cox-2(-/-) and Cox-1(-/-) knockout mice. These results indicate that cyclooxygenase-derived prostanoids are not major players in colitis-associated cancer. In contrast, tumor formation induced by multiple injections of AOM (with no DSS induced colitis) did not occur in Cox-2(-/-) knockout mice. Our data suggest that the mechanism of colorectal tumor promotion in colitis-associated cancer differs from the mechanism of tumor promotion for hereditary and sporadic colorectal cancer.
详细资料
- 文献种类:期刊
- 期刊名称: Carcinogenesis
- 期刊缩写: Carcinogenesis
- 期卷页: 2010年
- 地址: Department of Molecular and Medical Pharmacology, Department of Biological Chemistry, Molecular Biology Institute, and Jonsson Comprehensive Cancer Center, David Geffen School of Medicine, UCLA, Los Angeles, CA, USA
- ISBN: 0143-3334
- 备注:PMID:20061361
标签

Colon cancer mouse model
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