人原发性肝癌中p16基因表达及CpG岛甲基化状态的研究  

p16 Gene Expression and Methylation Status of CpG Island in Huaman Primary Hepatocellular Carcinoma

作　　者：刘建余[1] 覃扬[1] 李波[2] 孙芝琳[1] 孙泽芳[1] 

机构地区：[1]四川大学华西基础医学与法医学院医学分子生物学开放实验室,成都610041 [2]四川大学华西医院普外科

出　　处：《华西医科大学学报》2002年第4期540-543,共4页Journal of West China University of Medical Sciences

基　　金：国家自然科学基金资助 (批准号 3 9670 70 2 )

摘　　要：目的　进一步探讨人原发性肝癌中 p16基因 m RNA转录水平变化与其基因启动子区 Cp G岛甲基化的关系 ,及其在肝癌发生中的意义。方法　采用狭缝印迹杂交检测 2 0例人原发性肝癌及相应的癌旁、远癌组织及 2例正常人肝组织中 p16基因 m RNA表达水平 ,以甲基化特异性 PCR分析各组织中 p16基因启动子区 Cp G岛的甲基化状况 ,并进行统计分析。结果　 2 0例人原发性肝癌中 14例 (70 % ) p16 m RNA水平比远癌组织显著降低 ;13例 (6 5 % )显示 p16基因启动子区 Cp G岛甲基化 ,其中 84 .6 % (11例 )伴 p16 m RNA转录水平降低。结论　人原发性肝癌中存在高频率的 p16基因表达失活 ,其主要机制可能是启动子区 Cp G岛甲基化抑制了基因的转录 ,在人原发性肝癌的发生发展中有重要作用。其临床诊断和治疗意义有待进一步深入研究。Objective To find out the relativity of the diversity of p16 gene mRNA transcription level and methylation of CpG island in the gene promoter region in human primary hepatocellular carcinoma, as well as their significance in hepatocarcinogensis. Methods p16 mRNA level in cancerous, para cancerous, non cancerous and 2 normal liver tissues were semi quantified by Northern Slot Blot; methylation status of CpG island in p16 gene promoter region was studied by methylation specific PCR. The data were statistically analyzed. Results Fourteen of 20 (70%)human primary hepatocellular carcinomas showed obviously reduced p16 mRNA expression, compared with non cancerous tissue; 13 cases(65%) showed that the CpG island in gene promoter region was methylated, and 84.6% (11 cases) of them showed reduced p16 mRNA expression in cancerous tissues. Conclusion There was high frequency of p16 gene inactivation in human primary hepatocellular carcinoma and the major mechanism might be down regulation of p16 gene transcription and expression by aberrant methylation of CpG island in the gene promoter region, which might play an important role in human hepatocarcinogensis.

关 键 词：人肝细胞癌 P16基因 mRNA CPG岛 甲基化 

分 类 号：R735.7[医药卫生—肿瘤]