癌变·畸变·突变2018，Vol.30Issue(3)：182-187,6.DOI:10.3969/j.issn.1004-616x.2018.03.004
肥胖小鼠胰腺组织肿瘤相关基因突变频率的分析
Mutation frequencies of tumor-related genes in the pancreatic tissues of diet-induced obese mice
摘要
Abstract
OBJECTIVE:To detect expression of mutations in tumor-related genes,such as Kras,Trp53 and Smad4 in pancreatic tissues of diet-induced obese mice and to explore whether obesity is associated with genome instability in the pancreas.METHODS:Male C57BL/6 mice were fed normal chow diet and high-fat diet for 24 weeks.The body weight,food intake,body composition and plasma lipid were measured.Pancreatic genomic DNA was extracted and the exon 2 of Kras,exon 8 of Trp53 and exon 9 of Smad4 were amplified by using high-fidelity PCR.The PCR products were then subjected to the Sanger sequencing protocol.Cell proliferation was assessed by qPCR and immunohistochemistry for Ki67.RESULTS:Intake of 24 weeks of high-fat diet led to severe obesity in mice.High-fat diet feeding increased the body weight,fat mass,lean mass,hepatosomatic index and body-fat ratio of epididymal (P＜0.05).Body weight gain in high-fat diet group was significantly higher than those of chow diet group from eating the same weight of food(P＜0.05).Plasma lipid such as triglyceride,total cholesterol and low density lipoprotein cholesterol were significantly higher in high-fat diet group(P＜0.05).Moreover,the level of Ki67 mRNA was increased in the high-fat diet group(P＜0.05).There were several Ki67 positive cells in pancreatic duct,indicating that proliferation of pancreatic cells in obese mice were elevated.We detected 1 locus mutation in the Kras gene in 1 out of 50 samples (rate:2％).There was no mutation in the other two genes.CONCLUSION:Obesity resulted in instability of Kras gene in pancreatic tissue,which could play a role in the initiation and progression of pancreatic cancer.关键词
肥胖/胰腺癌/基因突变/小鼠Key words
obesity/pancreatic cancer/mutation/mice分类
医药卫生引用本文复制引用
王萍,刘冰峰,杨云风,蔡羽薇,谭娜,姚丽娟,罗燃燃,张果..肥胖小鼠胰腺组织肿瘤相关基因突变频率的分析[J].癌变·畸变·突变,2018,30(3):182-187,6.基金项目
国家自然科学基金(81573146,91539125) （81573146,91539125）
湖北省自然科学基金(2015CFB300) （2015CFB300）
