【作者】 赵国强；

【导师】 董子明；

【作者基本信息】 郑州大学 ， 病理学与病理生理学， 2005， 博士

【摘要】 癌基因(Oncogene)、抑癌基因(tumor suppressor gene)以及DNA修复基因(DNA repair gene)等肿瘤相关基因是细胞癌变的分子基础，从分子水平研究肿瘤的发生发展机制已成为众多分子生物学家和肿瘤学家研究的热点。DNA聚合酶β(DNA polymerase beta，pol β)是DNA聚合酶家族的一员，其DNA序列高度保守，为一看家基因，广泛分布于哺乳动物细胞内。pol β的主要功能是参与DNA修复，其表达水平在整个细胞周期中相对稳定，不受细胞周期增殖的调控。作为一种重要的DNA修复酶，pol β尤其是对1-4碱基突变进行切除修复(base excision repair，BER)，并且还具有跨损伤修复的功能。近年来国外有报道在结直肠癌、前列腺癌、乳腺癌、肝癌、肺癌、膀胱癌、食管癌中发现pol β基因的突变，其中结直肠癌患者中突变频率高达70-80％。pol β基因突变多发生在粘膜性恶性肿瘤，并且突变发生频率也相对较高。胃癌是我国发病率和死亡率最高的恶性肿瘤之一，亦属粘膜性恶性肿瘤，胃癌中pol β基因突变的研究尚属起步阶段，仅有日本学者一篇报道。研究发现很多的肿瘤中pol β基因和蛋白质高表达，在前列腺癌、乳腺癌、卵巢癌和结肠癌中发现pol β基因的表达量比癌旁正常组织高数倍到数十倍。然而胃癌组织中pol β基因的表达水平如何，国内外未见报道。幽门螺杆菌(Helicobacter pylori，Hp)的重要致病因子CagA(cytotoxin associated protein CagA)可引起DNA的氧化损伤，因此，推测胃癌发生过程中CagA与pol β基因突变和基因表达可能存在一定关系。 本研究利用分子生物学方法，检测和分析42例胃癌标本的胃癌组织、癌旁组织，15例正常人胃组织和胃癌细胞株(BGC823)pol β基因的突变情况及表达水平；检测胃癌病例和正常人胃组织Hp和CagA~+ Hp感染情况：构建野生型、胃癌来源突变型pol β表达载体；并将其转入NIH3T3细胞，初步观察其生物学效更多还原

【Abstract】 Oncogene, tumor suppressor gene and DNA repair gene constitute the molecular foundation of cell carcinogenesis . To study the development mechanism of turner from molecular level has become a more and more hot topic for many biologists and oncologists. DNA polymerase beta (DNA polβ )is a housekeeping gene and one member of DNA polymerase family. DNA sequence of DNA polβ is high conservative. DNA polβ gene exists extensively in mammalian cells. It’s main function is to repair damaged DNA. The expression level of DNA polβ is relatively stable in the whole cell cycle without being regulated by proliferation of cell cycle. As an important repairing enzyme, DNA polβ excises and repairs DNA base mutations ranged from 1 to 4 bases especially, that is the function of BER. Transleisional DNA synthesis is another function. Recently, it has been reported that DNA polβ gene mutations have been discovered in colorectal cancer, esophageal cancer, breast cancer, liver cancer, lung cancer, bladder cancer and prostate cancer. The mutation rate of DNA polβ is much higher in colorectal cancer, approximately 70-80%. The mutations usually occur in mucous malignant cancer and the mutation rate is increased significantly. Gastric carcinoma is one of the most common malignant tumors and it’s mortality rate is the highest in China. Of course, it belongs to mucosa malignant tumors. But there is no exploration on DNA polβ in gastric cancer except one report made by Japanese researchers. The expressions of DNA polβ have been detected in many tumors, such as: prostate cancer, breast cancer, ovarian cancer, colon cancer, and so on. Expression level is much higher in tumor tissue than that in corresponding更多还原