HPV-18病毒E2、E6与Brd4在宫颈癌及癌前病变的表达与意义  

Expression of human papillomavirus-18 E6,E2 and cellular bromodomain protein Brd4 in cervical intraepithelial neoplasia and cervical carcinoma

作　　者：黄卓敏[1] 江曼茹 古衍[1] 姚吉龙[1] 谢建生[2] 

机构地区：[1]南方医科大学附属深圳市妇幼保健院妇科,广东深圳518028 [2]南方医科大学附属深圳市妇幼保健院中心实验室,广东深圳518028

出　　处：《中国现代医学杂志》2012年第18期32-36,共5页China Journal of Modern Medicine

基　　金：深圳市科技计划项目(No:201003104)

摘　　要：目的探讨HPV-18病毒E2、E6与宿主蛋白Brd4在CIN和宫颈癌中的表达与临床意义。方法 RT-PCR检测HPV-18阳性的宫颈炎15例、CINⅠ19例、CINⅡ17例、CINⅢ20例、宫颈浸润癌24例的标本中E2和E6mRNA的表达,Western blot检测E2蛋白和Brd4的表达,比较上述指标在各组中的表达差异。结果 HPV-18E2和E6 mRNA在宫颈炎和CINⅠ的表达差异无显著性(P>0.05);从CIN到宫颈浸润癌,E2 mRNA的表达呈下降趋势;E6 mRNA的表达呈增加趋势(P<0.05);E6 mRNA和E2 mRNA的表达呈负相关(P<0.01)。E2蛋白和Brd4在宫颈炎和CINⅠ的表达差异无显著性(P>0.05);从CIN到宫颈浸润癌,其表达呈下降趋势(P<0.05)。结论 Brd4-E2复合体的解体,E2的表达缺失和E6的过度表达,可能是HPV-18诱导宫颈细胞恶性转型的关键环节,在宫颈癌的演变中起重要作用。检测HPV-18E2、E6与Brd4的表达对早期预测CIN的预后有一定的参考价值。To investigate the expression of human papillomavirus-18 E2, E6 and cellular bromod- omain protein Brd4 in cervical lesions and the role of which in cervical carcinogenesis and its potential clinical sig- nificance. [Methods] The expression of E2 and E6 mRNA in the tissues of 15 cases of cervicitis, 19 cases of CIN I , 17 cases of CIN II, 20 cases of CINII[ and 24 cases of invasion cervical carcinoma with HPV-18 infection was detected by reverse transcription polymerase chain reaction, meanwhile westernblot was applied to detect E2 protein and Brd4 in such cervical lesions. [ Results ] No significant differences of E2 and E6 mRNA expression were found between groups of cervicitis and CIN I （P 〉0.05）. However, the expression of E2 mRNA decreased dramatically cor- responding with pathological upgrading, meanwhile the expression of E6 mRNA increased inversely from groups of CIN to invasion cervical carcinoma （P 〈0.05）. The expression of E6 mRNA was inversely correlated with expression of E2 mRNA （r =-0.728, P 〈0.01）. No significant differences of E2 protein and Brd4 expression were found between groups of cervicitis and CIN I （P 〉0.05）, whereas the expression of E2 protein and Brd4 decreased significantly cor- responding with pathological upgrading from groups of CIN to invasion cervical carcinoma （P 〈0.05）. [ Conclusion ]Deletion of HPV-lg E2 and over expression of E6 induced by degradation of Brd4-E2 complex has been proved to be a key step in the malignant transformation of cervical ceils inducted by HPV, which may play an important role in cervical carcinogenesis. Therefore, detection of the levels of HPV-18 E2,E6 and Brd4 expression might be clini- cally valuable for the prediction of cervical carcinogenesis and the evaluation of prognosis in CIN.

关 键 词：人乳头瘤病毒18 E2 E6 Brd4 宫颈上皮内瘤变 宫颈癌 

分 类 号：R737.33[医药卫生—肿瘤]