|
- 2016
CDH1基因在SD大鼠舌黏膜癌变过程中甲基化和突变的研究
|
Abstract:
摘要 目的:通过甲基化和外显子突变研究探索CDH1基因在舌鳞状细胞癌发生过程中的作用。方法:采用质量分数为0.004%的4-硝基喹啉-1-氧化物(4-nitroquinoline-1-oxide,4NQO)饮水饲养90只无特定病原体(specific pathogen free,SPF)SD大鼠以诱发舌黏膜癌变全过程,分别于第10、14、18、22、24周分批处死大鼠,取舌黏膜组织行病理分级,并提取基因组DNA。利用甲基化特异性PCR(methylation-specific PCR,MS-PCR)检测CDH1启动子甲基化水平;利用聚合酶链式反应(polymerase chain reaction,PCR)扩增CDH1外显子1-16,提纯后测序以检测突变。结果:病变各阶段均未检测出CDH1启动子甲基化产物,CDH1 mRNA第2106位发生碱基G→T错义突变。结论:4NQO饮水诱导SD大鼠舌黏膜癌变的发生、发展可能与CDH1外显子突变有关而与CDH1启动子甲基化无关
[1] | Watt FM, Hogan BL. Out of Eden: stem cells and their niches [J]. Science, 2000, 287(5457)∶1427-30Suva ML, Riggi N, Bernstein BE. Epigenetic reprogramming in cancer[J]. Science, 2013, 339(6127)∶1567-1570 |
[2] | Hajra KM, Fearon ER. Cadherin and catenin alterations in human cancer[J]. Genes Chromosomes Cancer, 2002;, 34(3)∶255-268 |
[3] | Tamura G, Yin J, WangS, et al.E-cadherin gene promoter hypermethylation in primary human gastric carcinomas[J]. J Natl Cancer inst, 2000; 92(7)∶569 -573 |
[4] | Pogribny IP, Muskhelishvili L, Tryndyak VP, et al. The role of epigenetic events in genotoxic hepatocarcinogenesis induced by 2-acetylaminofluorene[J]. Mutat Res, 2011, 722(2)∶106-113 |
[5] | Gautier EL, Huby T, Saint-Charles F, et al. Enhanced dendritic cell survival attenuates lipopolysaccharide-induced immunosuppression and increases resistance to lethal endotoxic shock[J]. Journal of immunology, 2008, 180(10)∶6941-6946 |
[6] | Smogorzewska A, De Lange T. Different telomere damage signaling pathways in human and mouse cells[J]. EMBO J, 2002, 21(16)∶4338- 4348 |
[7] | Kanojia D, Vaidya MM. 4-nitroquinoline-1-oxide induced experimental oral carcinogenesis[J]. Oral Oncol, 2006, 42(7)∶655-667 |
[8] | Chen Q, Lipkina G, Song Q, et al. Promoter methylation regulates cadherin switching in squamous cell carcinoma[J]. Biochem Biophys Res Commun, 2004, 315(4)∶850-860 |
[9] | Saintigny P, Zhang L, Fan YH, et al. Gene expression profiling predicts the development of oral cancer [J]. Cancer Prev Res (Phila), 2011, 4(2)∶218- 229 |
[10] | Spiotto MT, Pytynia M, Liu GF, et al. Animal models to study the mutational landscape for oral cavity and oropharyngeal cancers[J]. J Oral Maxillofac Res, 2013, 4(1)∶1-14 |
[11] | 王治平,赵建江,陈中利,韩久松,郑俊发. 大鼠舌鳞癌诱变过程中MMP-3、TIMP-1的表达变化及相关性研究[J]. 口腔医学研究,2012,07∶651-655 |
[12] | Niwa T, Yamashita S, Tsukamoto T, et al. Whole-genome analyses of loss of heterozygosity and methylation analysis of four tumor-suppressor genes in N-methyl-N'-nitro-N-nitrosoguanidine induced rat stomach carcinomas[J]. Cancer Sci, 2005, 96(7)∶409-413 |
[13] | Monika Z, Ferreira AM, Czopek JP, et al. CDH1 gene promoter hypermethylation in gastric cancer: relationship to Goseki grading, microsatellite instability status, and EBV invasion[J]. Diagn Mol Pathol, 2006, 15(1)∶24-29 |