宫颈癌组织中人乳头瘤病毒16型E7蛋白致癌机理初探

Study on the carcinogenic mechanism of human papillomavirus type16 E7 protein in cervical carcinoma

目的 研究宫颈癌组织中人乳头瘤病毒 (HPV) 16 E7蛋白对视网膜母细胞瘤基因(Retinoblastoma)Rb蛋白及E2F 1的作用的机制 ,探讨HPV16 E7蛋白与宫颈癌发生的关系。方法 采用聚合酶链反应检测宫颈癌及正常宫颈组织中HPV16感染率 ,用蛋白印迹技术对HPV16DNA阳性的宫颈癌组织中是否存在HPV16 E7蛋白和R6蛋白 E2F 1形成的复合物进行检测。正常宫颈组织作为对照。结果 6 7例宫颈癌组织中HPV16DNA阳性率 5 0 .7% ;蛋白免疫印迹证实在正常宫颈组织中存在Rb蛋白 E2F 1复合物 ,用同法证实在宫颈癌组织中 ,HPV16 E7蛋白与Rb蛋白结合 ,并发现了部分E2F 1呈游离状态。结论 HPV16 E7蛋白在宫颈癌的发生过程中系通过与Rb E2F 1复合物中的Rb蛋白结合 ,使该复合物解离 ,导致细胞周期调控紊乱 ,进而引起细胞恶变。

Objective To determine the relationship between HPV16 E7 Rb protein binding(Rb protein was dissociated from pRb E2F 1complex)and the occurrence of cervical carcinoma.Methods HPV16 DNA in fection rate was tested in cervical carcinoma and normal cervical tissues by polymerase chain reaction(PCR)technique. Then using Western blot analysis to find the presence HPV16E7 protein and pRb E2F 1complex in HPV16 DNA positive cervical carcinoma tissues. The normal cervical tissues were used as control.Results Out of 67 samples with cervical carcinormas, 34 samples were HPV16 DNA positive(50.7%),no HPV16 DNA were detected in 10 samples of normal cervical tissues. In cervical carcinoma tissues, the HPV16E7 pRb complex, the free E2F-1 were detected by Western blot,but no complex of pRb E2F 1 was found.Conclusion Our results seem to suggest that HPV 16 E7 protein could interact with pRb through separating the complex of pRb E2F 1,release free E2F 1,resulted in disordered cell cycle and cell malignant transformation.