Wang Yun, Luo Bing, Yan Li-Ping, Huang Bao-Hua, Zhao Peng
Department of Microbiology, Qingdao University Medical College, Number 38 of Dengzhou Road, Qingdao 266021, Shandong Province, China.
World J Gastroenterol. 2005 Jun 7;11(21):3234-9. doi: 10.3748/wjg.v11.i21.3234.
To investigate the interrelationship between Epstein-Barr virus (EBV)-encoded proteins and cell proliferation, apoptosis and apoptosis-related proteins in gastric carcinoma, and to explore their role in gastric carcinogenesis.
Tissues from 13 cases of EBV-associated gastric carcinoma (EBVaGC) and 45 cases of matched EBV-negative gastric carcinoma (EBVnGC) were collected, and then subjected to analysis for apoptotic index (AI) using the terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end-labeling (TUNEL) assay. Nuclear cell proliferation-associated antigen ki-67 index (KI), bcl-2, and p53 expression were examined by immunohistochemistry. p53 mutation in exons 5-8 of 13 EBVaGC cases was determined by single-strand conformation polymorphism (SSCP) and DNA sequencing. RT-PCR and Southern hybridization were used to detect the expression of nuclear antigens (EBNAs) 1 and 2, latent membrane protein (LMP) 1, immediately early gene BZLF1 and early genes BARF1 and BHRF1 in 13 EBVaGC cases.
The percentage of AI, KI and p53 overexpression was significantly lower in the EBVaGC group than in the EBVnGC group. However, bcl-2 expression did not show significant difference between the two groups. p53 gene mutations were not found in 13 EBVaGCs. Transcripts of EBNA1 were detected in all 13 EBVaGCs, while both EBNA2 and LMP1 mRNA were not detected. Six of the thirteen cases exhibited BZLF1 transcripts and two exhibited BHRF1 transcripts. BARF1 mRNA was detected in six cases.
Lower AI and KI may reflect a low biological activity in EBVaGC. EBV infection is associated with p53 abnormal expression but not bcl-2 protein in EBVaGC. BZLF1, BARF1, and BHRF1 may play important roles in inhibiting cell apoptosis and tumorigenesis of EBVaGC through different pathways.
研究爱泼斯坦-巴尔病毒（EBV）编码蛋白与胃癌细胞增殖、凋亡及凋亡相关蛋白之间的相互关系，探讨它们在胃癌发生中的作用。
收集13例EBV相关胃癌（EBVaGC）组织及45例配对的EBV阴性胃癌（EBVnGC）组织，采用末端脱氧核苷酸转移酶（TdT）介导的dUTP-生物素缺口末端标记（TUNEL）法分析凋亡指数（AI）。通过免疫组织化学检测细胞核增殖相关抗原ki-67指数（KI）、bcl-2和p53表达。采用单链构象多态性（SSCP）和DNA测序法检测13例EBVaGC病例第5-8外显子的p53突变。应用逆转录-聚合酶链反应（RT-PCR）和Southern杂交检测13例EBVaGC病例中核抗原（EBNAs）1和2、潜伏膜蛋白（LMP）1、即刻早期基因BZLF1以及早期基因BARF1和BHRF1的表达。
EBVaGC组的AI、KI百分比及p53过表达率显著低于EBVnGC组。然而，两组间bcl-2表达无显著差异。13例EBVaGC中未发现p53基因突变。13例EBVaGC均检测到EBNA1转录本，而未检测到EBNA2和LMP1 mRNA。13例中有6例出现BZLF1转录本，2例出现BHRF1转录本。6例检测到BARF1 mRNA。
较低的AI和KI可能反映EBVaGC的低生物学活性。EBV感染与EBVaGC中p53异常表达有关，但与bcl-2蛋白无关。BZLF1、BARF1和BHRF1可能通过不同途径在抑制EBVaGC细胞凋亡和肿瘤发生中发挥重要作用。
