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[爱泼斯坦-巴尔病毒基因在爱泼斯坦-巴尔病毒相关胃癌中的表达]

[Expression of Epstein-Barr virus genes in EBV-associated gastric carcinoma].

作者信息

Wang Yun, Luo Bing, Zhao Peng, Huang Bao-Hua

机构信息

Department of Microbiology, Qingdao University Medical College, Qingdao, Shandong, 266021, P.R.China.

出版信息

Ai Zheng. 2004 Jul;23(7):782-7.

Abstract

BACKGROUND & OBJECTIVE: Epstein-Barr virus (EBV) is associated with the development of many malignant tumors. The forms of EBV and the expression of EBV genes in Burkitt's lymphoma and nasopharyngeal carcinoma (NPC) have been reported. These studies showed that the forms of EBV and the expression of EBV genes are various in different types of malignancies. However, there were only a few reports about the expression of EBV genes, especially the lytic genes, in gastric carcinoma tissues. This study was to determine the expression of EBV latent and lytic infection genes in gastric carcinoma at the transcriptional level by RT-PCR and Southern hybridization,and investigate the relationship between EBV-encoded genes and the tumorigenesis of gastric carcinoma at the molecular level.

METHODS

One hundred and eighty-five gastric carcinoma and corresponding para-carcinoma tissues were tested for EBV genome by polymerase chain reaction (PCR)-Southern analysis. EBV-encoded small RNA 1 (EBER1) of the PCR positive specimens was determined by in situ hybridization (ISH). Gastric carcinoma with positive EBER1 signals was confirmed EBV- associated gastric carcinoma (EBVaGC). RT-PCR and Southern hybridization were used to determine the expression of nuclear antigen (EBNA) promoters (Qp, Wp and Cp), EBNA 1 and 2,latent membrane protein (LMP) 1, 2A, and 2B and lytic genes (immediate-early genes BZLF1 and BRLF1, early genes BARF1 and BHRF1, late genes BcLF1 and BLLF1) in EBVaGCs.

RESULTS

There were 13 EBV positive samples in gastric carcinomas (7.03%), but no EBV positive sample in corresponding para-carcinomas. The transcripts of Qp were detected in all of the 13 EBVaGCs tissues, while both Wp and Cp were silent. All of the 13 cases expressed EBNA1 mRNA, but no EBNA2, LMP1, and LMP2B mRNA. LMP2A mRNA was detected in 5 of the 13 cases. Of the 13 EBVaGCs, 7 exhibited BcLF1 transcript and 2 exhibited BHRF1 transcript. The transcripts of BZLF1 were detected in 6 cases, and those of BARF1 also in 6 cases. No BLLF1 and BRLF mRNA were detected in the 13 EBVaGCs.

CONCLUSIONS

The latent pattern of EBV in EBVaGCs corresponds to the latency I or unique latency I/II, intermediate between the latency I and II. Part of lytic infection genes are expressed in EBVaGCs tissues. BARF1 and BHRF1 genes express in part of gastric carcinomas and their roles in gastric tumorigenesis need to be further studied.

摘要

背景与目的

爱泼斯坦-巴尔病毒(EBV)与多种恶性肿瘤的发生有关。已有关于EBV在伯基特淋巴瘤和鼻咽癌(NPC)中的形式及EBV基因表达的报道。这些研究表明,EBV的形式和EBV基因的表达在不同类型的恶性肿瘤中各不相同。然而,关于EBV基因,尤其是裂解基因在胃癌组织中的表达报道较少。本研究旨在通过逆转录聚合酶链反应(RT-PCR)和Southern杂交在转录水平检测EBV潜伏和裂解感染基因在胃癌中的表达,并在分子水平探讨EBV编码基因与胃癌发生的关系。

方法

采用聚合酶链反应(PCR)-Southern分析检测185例胃癌及相应癌旁组织中的EBV基因组。通过原位杂交(ISH)检测PCR阳性标本中的EBV编码小RNA 1(EBER1)。EBER1信号阳性的胃癌确诊为EBV相关胃癌(EBVaGC)。采用RT-PCR和Southern杂交检测EBVaGC中核抗原(EBNA)启动子(Qp、Wp和Cp)、EBNA 1和2、潜伏膜蛋白(LMP)1、2A和2B以及裂解基因(立即早期基因BZLF1和BRLF1、早期基因BARF1和BHRF1、晚期基因BcLF1和BLLF1)的表达。

结果

胃癌中有13例EBV阳性样本(7.03%),而相应癌旁组织中无EBV阳性样本。13例EBVaGC组织均检测到Qp转录本,而Wp和Cp均沉默。13例均表达EBNA1 mRNA,但未检测到EBNA2、LMP1和LMP2B mRNA。13例中有5例检测到LMP2A mRNA。13例EBVaGC中,7例有BcLF1转录本,2例有BHRF1转录本。6例检测到BZLF1转录本,6例也检测到BARF1转录本。13例EBVaGC中未检测到BLLF1和BRLF mRNA。

结论

EBVaGC中EBV的潜伏模式对应于潜伏I型或独特的潜伏I/II型,介于潜伏I型和II型之间。部分裂解感染基因在EBVaGC组织中表达。BARF1和BHRF1基因在部分胃癌中表达,它们在胃癌发生中的作用有待进一步研究。

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