Genetic and Chemical Models of Colorectal Cancer in Mice.
Genetic and Chemical Models of Colorectal Cancer in Mice.
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DOI：
10.1007/s11888-010-0046-1
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发表时间：
2010-03-10
影响因子：
--
通讯作者：
Yang, Vincent W
中科院分区：
文献类型：
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作者：
Nandan, Mandayam O;Yang, Vincent W
结直肠癌（CRC）是一个重要的健康问题，因为它的相关死亡率。大多数CRC表现出Wnt信号通路的失调，这是由腺瘤性结肠息肉病肿瘤抑制基因（APC）的突变失活或β-连环蛋白的突变激活引起的。疾病进展伴随着KRAS癌基因和p53肿瘤抑制基因的额外突变。其他CRC是微卫星不稳定的，因为负责DNA错配修复的关键分子的突变失活或表观遗传沉默。本文综述了几种常见的结直肠癌小鼠模型，突出了上述抑癌基因或原癌基因的生殖细胞突变的后果。本文还讨论了化学致癌物对小鼠结肠直肠肿瘤形成的肠组织的不利影响。这些小鼠模型为理解CRC发病机制做出了重要贡献，也可能成为治疗干预的潜在载体。
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.