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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 and relationship of p53, mdm2, K-ras and proliferating cell nuclear antigen (PCNA) proteins in the course of carcinogenesis of experimental lung cancer. METHODS: Rat lung squamous cell carcinoma was induced with 3-methylcholanthrene (MCA) and diethylnitrosamine (DEN), and p53, mdm2, and K were detected by immunohistochemistry. Expression of ras gene and PCNA during carcinogenesis . RESULTS: The positive expression rates of squamous metaplasia, atypical hyperplasia, carcinoma in situ, early invasive carcinoma, and invasive carcinoma in the normal bronchial epithelium and cancer-inducing group were: 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%, the positive rate of various protein expressions increased with the progress of canceration. P53 was associated with the expression of K-ras and PCNA (P<0.05). The expression of p53 was highly correlated with that of mdm2 (P<0.01). Conclusion: p53 is a sensitive indicator of lung cancer initiation and progression. It may have synergistic effects with mdm2 and K-ras. Overexpression of K-ras and PCNA may be a marker of lung cancer invasion and poor prognosis.