DNMT1高表达在MNNG诱导哈萨克族食管上皮细胞恶性转化中的作用

doi:10.3969/j.issn.1004-616x.2017.06.011

Abstract

Abstract: OBJECTIVE:To explore the influence of the high expression of DNMT1 on MNNG-induced malignant transformation of Kazakh esophageal epithelial cell and to provide theoretical basis for pathogenesis of esophageal cancer. METHODS:Normal esophageal cells in culture were derived from Kazakh esophagus epithelium. MTT and clonal assays were conducted to determine the malignant transformation doses of MNNG. DNMT1 overexpression cells and the normal epithelial cells were exposed to MNNG for one hour. MTT and soft agar colony forming experiment were performed to observe the formation of cell colony under different exposure conditions and different multiplying rate. Nude mouse tumorigenicity assay was conducted to detect malignantly transformed cells. RESULTS:After treatment with MNNG (1.50×10^-5 mol/L), cells with high expression of DNMT1 were able to form colonies in soft-agar medium after the 27th generation in vitro. These cells also formed local mass in nude mice but pathological evaluation showed that the local mass had disorderly structure and without squamous cell carcinoma morphology. On the other hand,innoculation of epithelial cells with high expression of transformed cells induced tumors in nude mice which showed squamous cell carcinoma morphology. CONCLUSION:A malignant transformation model of Kazakh esophageal epithelial cell with high DNMT1 expression was successful established. In addition,the model showed that DNMT1 high expression could promote induction of malignant transformation by MNNG.

Key words: DNMT1 expression, malignant transformation, MNNG, esophageal epithelial cell, Kazakhstan

CLC Number:

R73-3

XU Yi, LI Xufeng, ZHANG Huixia, CHEN Yan. High expression of DNMT1 in MNNG-induced malignant transformation of Kazakh esophageal epithelial cell[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2017, 29(6): 460-466.

References

[1] WANG Y,ZHANG Y,HERMAN J G,et al. Epigenetic silencing of TMEM176A promotes esophageal squamous cell cancer development[J]. Oncotarget,2017,8(41):70035-70048.
[2] 艺兰,钟原. 厦门市居民2005-2014年食管癌死亡的流行病学研究[J]. 肿瘤防治研究,2016,(8):709-712.
[3] 孙盼盼,刘莉,平智广,等. 不同地区癌症发病分布特征及聚类分析[J]. 中国癌症杂志,2016,6:499-507.
[4] DHE-PAGANON S,SYEDA F,PARK L. DNA methyl transferasel:regulatory mechanisms and implications in health and disease[J]. lnt J Biochem Mol Biol,2011,2(1):58-66.
[5] 曾瑶池,胡敏予. 食物中N-亚硝基化合物与肿瘤关系的研究进展[J]. 中华肿瘤防治杂志,2008,15(2):151-155.
[6] SANNE R,PIA V L,RIKKE P S,et al. Alarm symptoms of upper gastrointestinal cancer and contact to general practice-A population-based study[J]. Scand J Gastroenterol,2015,50(10):1268-1275.
[7] 陈艳,张慧霞. 基于TALE技术的哈萨克族食管上皮DNA甲基转移酶1高表达细胞株模型的构建[J]. 癌变·畸变·突变. 2016,28(6):428-437.
[8] 孙树汉. 肿瘤的表观遗传学研究[J]. 中国肿瘤生物治疗杂志,2008,15(1):8-13.
[9] MCCABE M T,LOW J A,DAIGNAULT S,et al. Inhibition of DNA methyltransferase activity prevents tumorigenesis in a mouse model of prostate cancer[J]. Cancer Res,2006,66(1):385-392.
[10] 殷科,盛贤能,郭宇,等. DNMT1、DNMT3b在胃癌中的表达及其临床意义[J]. 现代实用医学. 2013,25(12):1386-1388.
[11] UNNIKRISHNAN A,PRYCHITKO T M,PATEL H V,et al. Folate deficiency regulates expression of DNA polymerase β in response to oxidative stress[J]. Free Radic Biol Med,2011,50(2):270-280.
[12] 高冰芳,杨悦,杨京京,等. Dnmt1、Caveolin-1在结直肠癌中的表达及其临床意义[J]. 辽宁医学院学报, 2013,32(1):9-12.
[13] THERESA D A,SYLVIA T,JENS H,et al. Selective inhibition of esophageal cancer cells by combination of HDAC inhibitors and Azacytidine[J]. Epigenetics, 2015,10(5):431-445.
[14] 郑希,胡杨,袁勇,等. 内源性亚硝胺在食管癌一级预防中的作用及意义[J]. 华西医学,2013,28(12):1945-1948.
[15] 孙振卿,闫慧明,贾彬. 从形态及功能研究MNNG诱导GES-1永生化细胞的恶性转化[J]. 中国现代医学杂志,2012,22(22):14-18.
[16] 张旭,方其根,李振宁,等. 裸鼠皮下种植性人头颈鳞癌模型的建立[J]. 中国口腔颌面外科杂志,2013,11(5):395-398.
[17] 侯柏龙,杜王琪,熊一融,等. 人宫颈癌SiHa细胞荷瘤裸鼠模型的建立及鉴定[J]. 温州医科大学学报,2016,46(2):92-96.
[18] YANAGIHARA K,TAKIGAHIRA M,TANAKA H,et al. Development and biological analysis of peritoneal metastasis mouse models for human scirrhous stomach cancer[J]. Cancer Sci,2005,96(6):323-332.
[19] CHEN Y K,CHANG W S,WU I C,et al. Molecular characterization of invasive subpopulations from an esophageal squamous cell carcinoma cell line[J]. Anticancer Res,2010,30(3):727-736.

High expression of DNMT1 in MNNG-induced malignant transformation of Kazakh esophageal epithelial cell

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