Establishment and Characterization of a Human Epstein-Barr Virus-Associated Gastric Carcinoma in SCID Mice

A transplantable human Epstein-Barr virus-associated gastric carcinoma (EBVaGC), designated KT, was propagated in severe combined immunodeficiency (SCID) mice for 12 passages. Mucin and cytokeratin expression and the Alu sequence in tumor DNA confirmed that the KT tumor was derived from human epithelial tissue. The identity of clonal EBV in the original and KT tumors was demonstrated by terminal repeat analysis of EBV DNA. The pattern of latency gene expression of EBV was the same in both tumors. EBER1 was presented similarly in tumor cell nuclei by in situ hybridization. Reverse transcription-PCR analysis also demonstrated Q-promoter-driven EBNA1 expression but not BZLF1, EBNA2, or LMP1 expression. Thus, the transplantable human EBVaGC KT retains the original EBV with the same latency gene expression and can serve as a model for this unique type of gastric carcinoma.

一株命名为KT的可移植性EB病毒相关性胃癌（Epstein-Barr virus-associated gastric carcinoma, EBVaGC）在重症联合免疫缺陷（severe combined immunodeficiency, SCID）小鼠中传代12次。通过黏蛋白、细胞角蛋白的表达特征以及肿瘤DNA中的Alu序列，证实KT肿瘤起源于人类上皮组织。对EBV DNA的末端重复序列分析结果显示，原始肿瘤与KT肿瘤中的EBV克隆型完全一致。二者的EBV潜伏基因表达模式相同；原位杂交实验表明，两种肿瘤的肿瘤细胞核内均以相似方式表达EBER1。逆转录聚合酶链反应分析也证实，二者均存在Q启动子驱动的EBNA1表达，却未检测到BZLF1、EBNA2及潜伏膜蛋白1（latent membrane protein 1, LMP1）的表达。综上，该可移植性人类EBVaGC KT模型保留了原始EBV及其一致的潜伏基因表达特征，可作为这类独特胃癌亚型的研究模型。