本文選題：p16腫瘤抑制基因(p16)　切入點(diǎn)：甲基化　出處：《青島大學(xué)》2016年博士論文

【摘要】：目的:通過檢測吸煙肺腺癌患者p16基因啟動子和外顯子1 Cp G島位點(diǎn)Hap II p16(后稱p16位點(diǎn)Cp G島)甲基化狀態(tài),探討肺腺癌發(fā)生過程中p16位點(diǎn)Cp G島甲基化與吸煙、DNA甲基轉(zhuǎn)移酶(DNMT)之間相互作用機(jī)制。方法:應(yīng)用免疫組化和原位雜交方法檢測p16蛋白和p16m RNA的水平。應(yīng)用甲基化特異性PCR方法及RT-PCR方法分析p16位點(diǎn)Cp G島甲基化狀態(tài)及DNMT活性。結(jié)果:只有10%(4/40)p16-陽性病例發(fā)現(xiàn)p16啟動子Cp G島的甲基化,而18例p16-陰性病例的甲基化率為36.7%。p16陽性和p16陰性病例的甲基化率之間有顯著性差異。89例肺腺癌中的50例吸煙者有17例出現(xiàn)p16啟動子Cp G島的甲基化,39例非吸煙者僅5例出現(xiàn)甲基化,其甲基化率之間的差異有顯著性。提示:吸煙可能與p16啟動子Cp G島的甲基化過程有關(guān)。此外,89例肺腺癌中的35例DNMT高活性者15例檢測到p16啟動子Cp G島的甲基化,而其余54例中僅7例檢測到p16啟動子Cp G島甲基化,二者甲基化率有顯著性差異。結(jié)論:p16啟動子CpG島甲基化可能使得p16表達(dá)受到抑制,從而有利于肺腺癌的發(fā)生。吸煙可能促進(jìn)了p16啟動子Cp G島的甲基化,或者依靠它在p16啟動子Cp G島甲基化位點(diǎn)對DNA轉(zhuǎn)移酶(DNMT)活性和代謝的影響而發(fā)揮作用。
[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.
【學(xué)位授予單位】：青島大學(xué)
【學(xué)位級別】：博士
【學(xué)位授予年份】：2016
【分類號】：R734.2

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