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同一个体食管癌变过程中p16甲基化、缺失和蛋白表达变化及其对细胞增殖的影响
Deletion, Methylation and Protein Expression of p16 Gene in Esophageal Carcinogenesis of the Same Patient and Its Effects on Prolixferation of Esophageal Cell Lines
【作者】 余炜伟；
【导师】 王立东；
【作者基本信息】 郑州大学 ， 内科学， 2006， 博士
【摘要】 研究背景 食管癌（Esophageal Cancer，EC）是世界上最常见的六大恶性肿瘤之一，具有显著的地域性分布差异，河南省林州市及其毗邻的辉县、安阳等地区是我国，也是世界上食管癌发病率和死亡率最高的地区之一。5年生存率仅为10％左右，预后极差。然而，如在早期阶段得到及时的治疗，其五年生存率可达到90％以上。因此，食管癌早期发现是临床治疗上提高治愈率的瓶颈因素之一。 我们及其它实验室最近的研究提示：食管癌变演进是多种基因变化先后累积或叠加综合作用的结果。肿瘤抑制基因p53-Rb系统变化是河南食管癌高发区人群食管癌变过程中发生频率最高的分子生物学改变；p53-Rb系统变化可能是河南食管癌高发区人群食管癌变最重要的分子机制。食管癌组织p16蛋白表达、缺失及甲基化可能是食管癌变最重要的分子基础之一。 肿瘤抑制基因p16编码的p16蛋白可结合CDK4或CyclinD-CDK4复合物，阻止RB蛋白磷酸化，在细胞周期G1／S限制点起关键负调控作用，目前认为其失活机制主要有：缺失、点突变及启动子区DNA的5’CpG岛甲基化。近年研究表明人类多种肿瘤中存在着较普遍的p16基因表达失活现象。甲基化是真核生物DNA的一
【Abstract】 BackgroundEsophageal cancer (EC) is one of the sixth most common malignant diseases in the world with a remarkable geographical distribution. Linzhou city (formerly Linxian) and nearby counties in Henan province have been well recognized as the highest incidence area for EC in the world. Prognosis for EC is very poor and the five-year survival rate is only about 10% for the patients at late or advanced stage. However, the five-year survival rate for early EC patients could be as high as 90%. Obviously, early detection for EC is the bottlenecks in improving the curative rate of EC.Recent results from our laboratory and others suggest that accumulation and/or synergetic effect of multiple genetic alternations contributing to multistage carcinogensis of EC. Alterations of tumor suppressor p53-Rb pathway (including p53, Rb, p16, p14) have been demonstrated as the most common molecular events occurred during esophageal multistage carcinogensis, suggesting that alterations of