实验性肺癌癌变过程中p53、mdm2、K-ras及PCNA蛋白的表达  

Expression of p53, mdm2, k-ras, and PCNA Gene during Carcinogenesis in Experimental Lung Cancer

作　　者：李小华[1] 陈德基[1] 江曼[1] 张玉霞[1] 叶波[1] 杨飞[1] 刁路明[1] 唐志佼[1] 夏东[1] 刘铭球[1] 

机构地区：[1]武汉大学医学院病理学教研室,湖北武汉430071

出　　处：《癌症》2001年第9期921-925,共5页Chinese Journal of Cancer

基　　金：国家自然科学基金(编号:39870305);湖北省教委重点课题(编号:97A050)

摘　　要：目的:探讨p53、mdm2(murinedoubleminute2)、K-ras及增殖细胞核抗原(proliferatingcellnuclearantigen,PCNA)蛋白在实验性肺癌癌变过程中的表达及其相互关系。方法:用致癌物3-甲基胆蒽(3-methylcholanthrene,MCA)及二乙基亚硝胺(diethylnitrosamine,DEN)诱发大鼠肺鳞状细胞癌,应用免疫组化方法检测p53、mdm2、K-ras基因及PCNA在癌变过程中的表达。结果:在对照组正常支气管粘膜上皮、诱癌组中鳞状化生及不典型增生、原位癌、早期浸润癌、浸润癌阶段各蛋白阳性表达率分别为:p53,0、33.33%、50.00%、60.00%、69.57%;mdm2,10.00%、11.11%、28.57%、46.67%、56.52%;K-ras,0、5.56%、21.43%、40.00%、43.48%;PCNA,20.00%、27.28%、35.71%、67.67%、82.61%,各种蛋白表达的阳性率随癌变进展而升高。p53与K-ras、PCNA的表达相关(P<0.05)。p53与mdm2的表达高度相关(P<0.01)。结论:p53是肺癌启动及进展的敏感指标,可能与mdm2、K-ras存在协同作用,K-ras及PCNA过度表达可能是肺癌浸润及预后不良的标志。Objective: To investigate the expression of p53, murine double minute 2 (mdm2), k ras, and proliferating cell nuclear antigen(PCNA) during carcinogenesis in induced rat′s lung cancer.Methods: Immunohistochemical S P method was used to examine the expression of p53, mdm2, k ras, and PCNA in induced squamous cell carcinoma of rats with 3 methylcholanthrene (MCA) and diethylnitrosamine (DEN). Results: In normal tissue of control group and the stage of squamous metaplasia and dysplasia of epithelium, carcinoma in situ, microinvasive carcinoma, invasive carcinoma, and the positive overexpression rates of p53 gene was 0, 33.33%, 50.00%, 60.00%,and 69.57%,respectively and the mdm2 was 10.00%,11.11%, 28.57%, 46.67%, and 56.52%,respectively; the k ras was 0, 5.56%, 21.43%, 40.00%, 43.48%; The PCNA was 20.00%, 27.78%, 35.71%, 67.67%, and 82.61%,respectively; the positive rates increased obviously when the carcinoma developed. The positive rates among p53, K ras, and PCNA were associated (P< 0.05), the high relationship was found between the expression of p53 and mdm2(P< 0.01).Conclusion: The promotion, progression, and invasion of lung squamous cell carcinoma were associated with the overexpression of p53, mdm2, k ras, and PCNA gene. These genes maybe have some synergetic effect on lung cancer. The level of expression of p53, mdm2, k ras, and PCNA were the molecular markers for early diagnosis and prognosis judgment of lung cancer.

关 键 词：实验性肺癌 免疫组织化学 P53 MDM2 K-RAS PCNA 基因表达 

分 类 号：R734.2[医药卫生—肿瘤]