Gan Runliang, Xie Xiaoli, He Jie, Liu Xiaomin, Hong Li, Tang Yunlian, Liu Fang, Xie Hailong
Cancer Research Institute, University of South China, Hengyang City, China.
Tumori. 2010 May-Jun;96(3):465-72. doi: 10.1177/030089161009600315.
The mechanisms of Epstein-Barr virus (EBV)-associated tumor development are incompletely understood. The aim of this study was to investigate the gene expression of EBV-associated lymphomas in hu-PBL/SCID mice.
Human peripheral blood lymphocytes (hu-PBL) from EBV-seropositive donors were transplanted into severe combined immunodeficiency (SCID) mice. In situ hybridization was used to detect EBV-encoded small RNA- 1 (EBER1) in tumor tissues. Mutation of TP53 exons 5-8 in EBV-induced lymphomas was analyzed by PCR-SSCP. Immunohistochemical staining was used to examine EBV gene products and cellular oncoproteins.
Twenty-one of 29 mice developed tumors. EBER1 was positive in the nuclei of almost all tumor cells. Immunohistochemistry showed positive staining of LMP1, EBNA2 and ZEBRA in a small number of tumor cells. Immunohistochemically detectable p53 protein expression was common (85.7%), but TP53 gene mutations were identified in only four cases (19.1%) of EBV-associated lymphomas. Positivity rates of C-myc, Bcl-2 and Bax expression were 100%, 95.2%, and 90.5%, respectively, in the 21 cases of EBV-associated lymphomas.
Our preliminary findings suggest that EBV-associated lymphomas in hu-PBL/SCID chimeras show EBV infection, expression of oncogenic viral genes, and overexpression of cellular oncogenes. TP53 gene mutations are rare but p53 protein is commonly expressed in EBV-associated lymphomas.
爱泼斯坦-巴尔病毒（EBV）相关肿瘤发生的机制尚未完全明确。本研究旨在探讨人外周血淋巴细胞-重症联合免疫缺陷（hu-PBL/SCID）小鼠中EBV相关淋巴瘤的基因表达情况。
将EBV血清阳性供体的人外周血淋巴细胞（hu-PBL）移植到重症联合免疫缺陷（SCID）小鼠体内。采用原位杂交技术检测肿瘤组织中EBV编码的小RNA-1（EBER1）。通过聚合酶链反应-单链构象多态性分析（PCR-SSCP）检测EBV诱导的淋巴瘤中TP53基因外显子5-8的突变情况。采用免疫组织化学染色检测EBV基因产物和细胞癌蛋白。
29只小鼠中有21只发生肿瘤。几乎所有肿瘤细胞的细胞核中EBER1均呈阳性。免疫组织化学显示少数肿瘤细胞中LMP1、EBNA2和ZEBRA呈阳性染色。免疫组织化学可检测到的p53蛋白表达常见（85.7%），但在仅4例（19.1%）EBV相关淋巴瘤中鉴定出TP53基因突变。在21例EBV相关淋巴瘤中，C-myc、Bcl-2和Bax表达的阳性率分别为100%、95.2%和90.5%。
我们的初步研究结果表明，hu-PBL/SCID嵌合体中EBV相关淋巴瘤表现出EBV感染、致癌病毒基因表达和细胞癌基因过表达。TP53基因突变罕见，但p53蛋白在EBV相关淋巴瘤中普遍表达。
