Investigation of abnomatily of cell cycle regulation and its clinical application in human lung cancer

为了探讨细胞周期调控的异常及其在肺癌中的临床应用，我们对肺癌手术标本进行了免疫组织化学染色和临床病理分析，2)对培养的肺癌细胞系进行了细胞生物学分析。1)细胞周期蛋白A的表达是增殖活性和患者预后不良的标志，II)肉瘤也是如此，III)细胞周期蛋白E的阳性也预示着腺癌的预后较差，但在鳞癌中预后较好，4)细胞周期蛋白E的阳性反映了非增殖细胞中蛋白质的积累，可能是细胞周期蛋白E降解下调的结果。2)从手术材料中建立了2个大细胞癌细胞系和3个小细胞癌细胞系，2)过表达cdc2或cdk2抑制PC12细胞的分化，3)同时下调cdc2和cdk2的活性，诱导PC12细胞分化；4)过表达CDK4诱导所有肺癌细胞系的凋亡。2的结果为肺癌的治疗提供了新的模式，通过给予细胞周期分子诱导细胞分化的凋亡来治疗肺癌。

To investigate the abnomatily of cell cycle regulation and its clinical application in human lung cancer, we performed 1) immunohistochemical staining with subsequent clinicopathological analysis on the surgical materials of lung cancer, 2) cell biological analysis using cultured cell lines of human lung cancer.1-I) expression of cyclin A serves as a marker of proliferative activity and patients' poor prognosis, ii) this was also true in sarcomoa, iii) cyclin E positivity also indicates worse prognosis in adenocarcinoma, but better prognosis in squamous cell carcinoma (SCC), iv) positivity of cyclin E in SCC reflects accumulation of protein in non-proliferating cells and may result from the downregulation of cyclin E degradation, iv) cdk-inhibitor serve as a assmbly factor for cyclin/cdk in low dose and activate its complex.2-I) Two cell lines of large cell carcinoma and 3 lines of small cell carcinoma were established from surgical materials, ii) overexpression of cdc2 or cdk2 suppressed differentiation of PC12 cells, iii) that simultaneous downregulation of cdc2 and cdk2 activity induces neuronal differentiation in PC12 cells iv) overexpression of cdk4 induced apoptosis in all cell lines of lung carcinoma.The results described in 1 showed diversity in the expression mechanism of cell cycle molecules depending on the histological type and utility of immunostaining of those protein for the evaluation of patients' prognosis in lung cancer. The results of 2 shed the light on the new mode of therapy for lung cancer by inducing apoptosis of cellular differentiation with administration of cell cycle molecules.