Baker S M, Harris A C, Tsao J L, Flath T J, Bronner C E, Gordon M, Shibata D, Liskay R M
Department of Molecular and Medical Genetics, Oregon Health Sciences University, Portland 97201, USA.
Cancer Res. 1998 Mar 15;58(6):1087-9.
Analysis of two human familial cancer syndromes, hereditary nonpolyposis colorectal cancer and familial adenomatous polyposis, indicates that mutations in either one of four DNA mismatch repair gene homologues or the adenomatous polyposis coli (APC) gene, respectively, are important for the development of colorectal cancer. To further investigate the role of DNA mismatch repair in intestinal tumorigenesis, we generated mice with mutations in both Apc and the DNA mismatch repair gene, Pms2. Whereas Pms2-deficient mice do not develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop approximately three times the number of small intestinal adenomas and four times the number of colon adenomas relative to Min and Pms2+/-;Min mice. Although Pms2 deficiency clearly increases adenoma formation in the Min background, histological analysis indicated no clear evidence for progression to carcinoma.
对两种人类家族性癌症综合征——遗传性非息肉病性结直肠癌和家族性腺瘤性息肉病的分析表明，四种DNA错配修复基因同源物中的任何一种发生突变，或分别是腺瘤性息肉病大肠杆菌（APC）基因发生突变，对于结直肠癌的发展都很重要。为了进一步研究DNA错配修复在肠道肿瘤发生中的作用，我们构建了Apc和DNA错配修复基因Pms2均发生突变的小鼠。虽然Pms2缺陷型小鼠不会发生肠道肿瘤，但Pms2缺陷且携带Apc等位基因Min杂合子的小鼠，相对于Min和Pms2+/-;Min小鼠，发生的小肠腺瘤数量约为其三倍，结肠腺瘤数量约为其四倍。虽然Pms2缺陷在Min背景下明显增加了腺瘤形成，但组织学分析表明没有明显的进展为癌的证据。
