【作者】 成静；

【导师】 伍钢；

【作者基本信息】 华中科技大学 ， 肿瘤学， 2007， 硕士

【摘要】 背景:近年来,CDK1的上游磷酸酶CDC25倍受关注。CDC25家族成员CDC25B能在细胞周期关键转换点使CDK脱磷酸化而激活,是早期有丝分裂的启动因子。Aurora激酶家族是新近发现与细胞有丝分裂密切相关的基因,是调节中心体、微管功能的丝/苏氨酸激酶。Aurora-A激酶的活性是CDK1-cyclinB在中心体的募集反应中必须的,而CDC25B的磷酸化是通过Aurora-A激酶完成的。研究发现两者均在多种恶性肿瘤中高表达。目的:探讨CDC25B、Aurora-A与肺癌发生、发展的关系,旨在寻找肺癌新的分子治疗靶点和肿瘤标志物,为指导肺癌个性化治疗提供一种新的办法。方法:采用SP法检测76例肺癌组织,11例肺良性病变组织中CDC25B、AuroraA的表达情况与肺癌临床病理参数之间的关系。采用RT-PCR及Western-blot方法检测Aurora A和CDC25BmRNA和蛋白表达。结果:免疫组化研究结果发现CDC25B、Aurora-A在76例非小细胞肺癌组织与11例肺良性病变组织中的阳性表达率分别是56. 9 %,64.6%和18. 2 %,22.4% ,两者比较差异均有统计学意义( P < 0. 01)。Western bolt检测结果与免疫组化检测Aurora-A、CDC25B蛋白表达结果趋于一致。RT-PCR检测30例非小细胞肺癌组织标本中Aurora-A mRNA和CDC25B mRNA表达水平高于相应癌旁组织,分别为63.3%和56.7%,癌组织与癌旁组织相比较差异有统计学意义(P < 0. 05)。结论:Aurora-A和CDC25B基因在临床非小细胞肺癌的标本中,都存在mRNA与蛋白水平的高表达。Aurora-A和CDC25B高表达有高度一致性。Aurora-A和CDC25B可能为判断非小细胞肺癌预后的有效指标。更多还原

【Abstract】 Background: Recently CDC25 family, which is the upstream phosphatase of CDK1 is significantly noticed by many scientists. The CDC25B phosphatases are involved in the dephosphorylation and activation of CDK-1 at the key cell cycle transitions. CDC25B acts as an initiator of the early mitotic events. Aurora-A, as a member found in recent years belonging to serine/threonine kinase family, proves relating to centresomes’maturation and chromosomes division. It has been confirmed as a new oncogene due to its high expression in multiple cancers cells, playing a key role in the normal process of mitosis as proved in previous researches. Aurora-A activity is required for the recruitment of CDK1-cyclin B1 to the centrosome prior to its activation and thecommitment of the cell to mitosis. CDC25B phosphorylation is dependent on Aurora-A. Recent researches found that Aurora-A and CDC25B over expresses in various malignancies.Objective: To explore the relationship between the expression of CDC25B or Aurora-A and the clinic pathological features of no small cell lung cancer. Provide a theoretical basis for screening tumor marker and molecular therapeutic target of lung cancer.Methods: Using SP immunohistochemistry methods, the expression of CDC25B and Aurora-A in 76 cases of non small cell lung cancer and 11 cases of benign lung disease was detected. The relationship between the expression of CDC25B or Aurora-A and the clinic pathological features of non small cell lung cancer was analyzed by the statistical method. Aurora A and CDC25B mRNA and protein expression were examined by reverse transcription–polymerase chain reaction (RT-PCR) and Western blot respectively.Results: In this research, over expression of CDC25B was found in 43/76 patients (56.9%) compared with their corresponding neighboring tissue (2/11, 18.2 %) through immunohistochemistry. Over expression of Aurora-A is 64.6% and 22.4% .with significant difference shown byχ2 test under SPSS 11.5(p﹤0.01). Implying the accordance in Aurora-A or CDC25B protein expression level between the result a from Western bolt and that from immunohistochemistry. In this research, the expression of Aurora-A and CDC25B in tumor in vivo from 30 cases of lung cancer patients was detected through RT-PCR. Over expression was observed in 19 cases (63.3%) /in 17 cases (56.7%) compared with corresponding neighboring tissues. as proven by Bandleader Analysis and Paired t-test under SPSS 11.5(p﹤0.05).Conclusions: Over expression of Aurora-A and CDC25B mRNA/protein is presents in vitro of non small cell lung cancer. Furthermore the over expression of Aurora-A and CDC25B is compact correlation. And both Aurora-A and CDC25B are all useful factors in predicting prognosis of patients with non small cell lung cancer.更多还原