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Detection of Epstein-Barr virus gene products, p53 protein and bcl-2 protein in nasopharyngeal carcinoma.

鼻咽癌中EB病毒基因产物、p53蛋白和bcl-2蛋白的检测

基本信息

批准号：
06454485
负责人：
FURUKAWA Mitsuru
金额：
$ 3.33万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1994
资助国家：
日本
起止时间：
1994 至 1995
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-06454485/
关键词：
NPC EBV EBERS BHLF1 p53 bcl-2 p53 EBウイルス BZLF1 BHLF1 p51 BMLF1

项目摘要

Nasopharyngeal carcinoma (NPC), an epithelial tumor which is characterized by marked geographic and population differences in incidence, is consistently associated with the Epstein-Barr virus (EBV). Within the tumor, the EBV DNA is homogeneous and clonal with regard to repeat sequences suggesting that the tumor is also clonal.In this work we examined to detect EBV in formalin-fixed paraffin-embedded NPC specimens by using both polymerase chain reaction (PCR) for EBV-DNA and in situ hybridization for EBV-encoded small RNAs (EBERs). EBV-DNA was detected in none of 3 keratinizing squamous cell carcinomas (SCC), 22 of 24 non-keratinizing carcinomas (NKC), all 13 undifferentiated carcinoma (UNPC) and none of 2 adenocarcinomas (AC). EBERs was detected in none of 5 SCC,30 of 32 NKC,16 of 17 UNPC and none of 2 AC.As an additional study in situ hybridization using BHLF oligonucleotide probes and immunohistochemistry using monoclonal antibodies against LMP1, EBNA2, BZLF1 protein, p53 protein and bcl-2 protein were performed in 56 primary NPC.LMP1 was detected in 17 cases (30%) whereas EBNA2 was not detectable. Bcl-2 protein was positive in 50 cases (89%), but its expression did not depend on expression of LMP1, which did not demonstrate induction of bcl-2 by LMP1 as seen in vitro. Cytoplasmic BZLF1 expression was detectable in 18 cases (32%) whereas BHLF was positive only in 6 cases (11%). This finding suggests BZLF1 which disrupts viral latency dysfunctions despite of its expression. p53 protein was positive in 31 cases (55%), and there was a distinct correlation between expression of BZLF1 and p53 protein (p<0.001). This finding suggests the interaction between BZLF1 and p53 which inactivates each other is one of tumorigenic factor in NPC

鼻咽癌(NPC)是一种具有显著地理和人群差异的上皮性肿瘤，其发病与EB病毒(EBV)密切相关。在肿瘤内，EBV DNA在重复序列方面是均一的和克隆的，这表明肿瘤也是克隆性的。在这项工作中，我们检测了福尔马林固定的石蜡包埋的鼻咽癌标本中的EBV-DNA检测EBV-DNA和EBV编码的小RNA(EBER)的原位杂交。3例角化性鳞状细胞癌(SCC)、22例非角化性鳞癌(NKC)、13例未分化癌(UnPC)和2例腺癌(AC)均未检出EBV-DNA。5例鳞癌、30例NKC、16例UnPC和2例非小细胞肺癌均未检测到EBERs。另一项研究是用BHLF寡核苷酸探针进行原位杂交，用抗LMP1、EBNA2、BZLF1蛋白、P53蛋白和bcl2蛋白的单抗进行免疫组织化学染色。50例(89%)BCL-2蛋白表达阳性，但其表达不依赖于LMP1的表达，在体外不能证明LMP1诱导BCL-2的表达。BZLF1胞浆阳性18例(32%)，BHLF阳性6例(11%)。这一发现表明，BZLF1尽管表达了BZLF1，但仍能破坏病毒的潜伏功能。P53蛋白阳性31例(55%)，且BZLF1与P53蛋白表达呈显著正相关(p&lt；0.001)。提示BZLF1与P53的相互作用是鼻咽癌的致癌因素之一。