Genetic and Chemical Models of Colorectal Cancer in Mice

小鼠结直肠癌的遗传和化学模型

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Abstract

Colorectal cancer (CRC) is a significant health concern because of its associated mortality. Most CRCs exhibit dysregulation of the Wnt signaling pathway, caused by mutational inactivation of the adenomatous polyposis coli tumor suppressor gene (APC) or mutational activation of β-catenin. Disease progression is accompanied by additional mutations in the KRAS oncogene and p53 tumor suppressor gene. Other CRCs are microsatellite unstable because of mutational inactivation or epigenetic silencing of key molecules responsible for DNA mismatch repair. This review focuses on several common mouse models of CRC, highlighting the consequences of germline mutation of the aforementioned tumor suppressor genes or proto-oncogenes. This article also discusses chemical carcinogens that adversely affect the intestinal tissues with formation of colorectal neoplasia in mice. These mouse models have significantly contributed to the understanding of the mechanisms responsible for CRC pathogenesis and also may serve as potential vehicles for therapeutic intervention.

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