结肠腺瘤样息肉病基因在结肠癌患者中的突变热点研究  

Mutation hotspot of adenomatous polyposis coli gene in patients with colon cancer

作　　者：崔凯[1] 王焕[2] 宰守峰[1] 冯衍生[3] 

机构地区：[1]新乡市中心医院普瘤外科,河南新乡453000 [2]新乡市中心医院肾内科,河南新乡453000 [3]新乡医学院基础医学院病理生理学教研室,河南新乡453003

出　　处：《新乡医学院学报》2015年第9期826-828,832,共4页Journal of Xinxiang Medical University

摘　　要：目的探讨结肠腺瘤样息肉病基因在结肠癌中的突变热点及对肿瘤的影响。方法通过公共数据库c Bioportal调取结肠癌突变位点结果,根据其中的一段突变热点区域,构建对应结肠腺瘤样息肉病基因过表达载体及RNAi,采用Western blot检测并证实此区域的功能。结果结肠腺瘤样息肉病基因在结肠癌中的突变率高达73.9%,显著高于其他肿瘤（P〈0.05）;其中3 454~4 662 bp区域突变发生率占总突变次数的56.1%;构建RNAi后在正常肠上皮细胞中发现β-catenin、CD44、Ki67出现显著上调;在结肠癌细胞中过表达野生型APC（wt-APC）,缺失APC（hotdelAPC）的情况下发现,wt-APC可以有效抑制c-myc、β-catenin、CD44、Ki67等致癌基因的表达,但hotdel-APC不能。结论APC基因中3 454~4 662 bp这段区域编码的蛋白可能在结肠癌发生过程中发挥重要作用。Objective To investigate the mutation hotspot of adenomatous polyposis coli（ APC） gene in colon cancer and its effect on tumor. Methods Mutation results were obtained through the public c Bioportal database retrieval of colon cancer,according to a one of the mutational hot spot regions,the corresponding APC over expression vector and RNAi were constructed,and western blot was used to detect and confirm the regional function. Results The mutation rate of APC gene in colorectal cancer was 73. 9%,it was significantly higher than that in other tumor（ P〈0. 05）; mutation rate in region of 3 454-4 662 bp accounted for 56. 1% of the total number of mutations. After constructing RNAi,it found that β-catenin,CD44 and Ki67 were significantly up-regulated in the normal intestinal epithelial cells; wild type APC（ wt-APC） was overexpressed in colon cancer cells,the expressions of c-myc,β-catenin,CD44,Ki67 were inhibited in colon cancer cells by wt-APC while this region of APC（ hotdel-APC） was deleted,but hotdel-APC did not. Conclusion 3 454- 4 662 bp APC gene in this region encoded proteins may play an important role in the process of development of colonic cancer.

关 键 词：结肠腺瘤样息肉病基因 结肠癌 突变热点 

分 类 号：R735[医药卫生—肿瘤]