DNA甲基转移酶在吸烟者肺腺癌p16基因启动子甲基化中的作用机制研究

发布时间：2018-03-30 05:07

  本文选题：p16肿瘤抑制基因(p16)　切入点：甲基化　出处：《青岛大学》2016年博士论文

【摘要】：目的:通过检测吸烟肺腺癌患者p16基因启动子和外显子1 Cp G岛位点Hap II p16(后称p16位点Cp G岛)甲基化状态,探讨肺腺癌发生过程中p16位点Cp G岛甲基化与吸烟、DNA甲基转移酶(DNMT)之间相互作用机制。方法:应用免疫组化和原位杂交方法检测p16蛋白和p16m RNA的水平。应用甲基化特异性PCR方法及RT-PCR方法分析p16位点Cp G岛甲基化状态及DNMT活性。结果:只有10%(4/40)p16-阳性病例发现p16启动子Cp G岛的甲基化,而18例p16-阴性病例的甲基化率为36.7%。p16阳性和p16阴性病例的甲基化率之间有显著性差异。89例肺腺癌中的50例吸烟者有17例出现p16启动子Cp G岛的甲基化,39例非吸烟者仅5例出现甲基化,其甲基化率之间的差异有显著性。提示:吸烟可能与p16启动子Cp G岛的甲基化过程有关。此外,89例肺腺癌中的35例DNMT高活性者15例检测到p16启动子Cp G岛的甲基化,而其余54例中仅7例检测到p16启动子Cp G岛甲基化,二者甲基化率有显著性差异。结论:p16启动子CpG岛甲基化可能使得p16表达受到抑制,从而有利于肺腺癌的发生。吸烟可能促进了p16启动子Cp G岛的甲基化,或者依靠它在p16启动子Cp G岛甲基化位点对DNA转移酶(DNMT)活性和代谢的影响而发挥作用。
[Abstract]:Objective: to detect the methylation status of p16 promoter and exon 1 CpG island Hap II p16 (p16 CpG island) in patients with lung adenocarcinoma. To investigate the interaction mechanism between methylation of p16 site CpG island and smoking DNA methyltransferase (DNMTT) in lung adenocarcinoma. Methods: the levels of p16 protein and p16m RNA were detected by immunohistochemistry and in situ hybridization. The methylation status and DNMT activity of CpG island at p16 site were analyzed by PCR and RT-PCR methods. Results: methylation of p16 promoter CpG island was found in only 10 / 4 / 40 / 40 p16- positive cases. The methylation rate of 18 p16-negative cases was significant difference between 36.7%.p16 positive and p16-negative cases. 17 of 50 smokers of 89 cases of lung adenocarcinoma had methylation of p16 promoter CP G island in 39 non-smokers. There were only 5 cases of methylation. The results showed that smoking may be related to the methylation process of p16 promoter CP G island. In addition, 35 cases of lung adenocarcinoma with high DNMT activity detected methylation of p16 promoter CP G island in 15 cases. In the other 54 cases, the methylation of p16 promoter CpG island was detected in only 7 cases, and there was significant difference in the methylation rate between them. Conclusion the methylation of CpG island of the p16 promoter may inhibit the expression of p16. Smoking may promote the methylation of p16 promoter CpG island, or it may play a role on the activity and metabolism of DNA transferase in the methylation site of p16 promoter CpG island.
【学位授予单位】：青岛大学
【学位级别】：博士
【学位授予年份】：2016
【分类号】：R734.2

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