Cyclin E、CDK2和p21WAF1在食管上皮癌变过程中的表达及意义

目的探讨食管上皮癌变过程中细胞周期调控因子cyclin E、CDK2和p21WAF1的表达状况及其意义.方法应用免疫组化SP法和原位杂交方法分别检测48例食管癌组织、31例非典型增生组织和17例正常食管粘膜中cyclin E、CDK2和p21WAF1蛋白及mRNA表达.应用半定量RT-PCR和Western blot检测22例新鲜食管癌及相应癌旁组织的mRNA和蛋白表达.结果从食管正常粘膜、非典型增生组织到癌组织,cyclin E和CDK2蛋白和mRNA阳性表达率逐渐上升,差异具有统计学意义(P＜0.01或P＜0.05).食管癌组织中cyclin E、CDK2和p21WAF1蛋白及mRNA高表达,与癌旁组织或切缘正常食管粘膜有显著性差异(P＜0.01).cyclin E、CDK2和p21WAF1基因表达显著正相关(P＜0.01或P＜0.05).结论食管上皮癌变过程中,细胞周期相关基因cyclin E和CDK2表达逐渐增强.cyclin E基因表达异常是食管癌变过程中的早期事件.p21WAF1基因在食管癌中高表达,可能与细胞周期调控的反馈机制有关.

The gene expressions of cyclin E, CDK2 and p21WAF1 and their significant in esophageal carsinogenesis

Objective To investigate the effects of the gene e xpressions of cyclin E, CDK 2 and p21 WAF1 in esophageal carcinogenesi s.Methods Immunohistochemical and in situ hybridization metho ds were applied to detect the expression of cyclin E,CDK 2 and p21 WAF1 proteins and mRNAs in 48 cases of esophageal carcinoma,31 cases of dysplasia and 17 cases of normal epithelium. Twenty two cases of fresh esophageal carcinom a tissue and corresponding adjacent noncancerous tissues were examined by wester n blot and semiquantitative RT-PCR for the protein and mRNA expressions for cyc lin E,CDK 2 and p21 WAF1.Results The positive rates of cyclin E and CDK 2 proteins and mRNAs were increased from normal epithelium to dysplasia and carcinoma tissu es gradually(P<0.01 or P< 0.05). Cyclin E,CDK 2 and p21 WAF 1 overexpressions were frequently found in esophageal carcinoma and there was very significant statistical difference between carcinoma and corresponding adja cent noncancerous tissue or normal epithelium (P<0.01). There was significan t positive correlation among cyclin E,CDK 2 and p21 WAF1gene expressio ns(P<0.01 or P< 0.05).Conclusion Elevated levels of cyclin E and CDK 2 are obser ved gradually during esophageal carcinogenesis. Abnormal expression of cyclin E is an early event in esophageal carcinogenesis. The overexpression of p21 WAF 1gene in esophageal carcinoma is probably due to the feedback control loop in cell cycle.