Pajic A, Staege M S, Dudziak D, Schuhmacher M, Spitkovsky D, Eissner G, Brielmeier M, Polack A, Bornkamm G W
Institut für Klinische Molekularbiologie und Tumorgenetik, Hämatologikum der GSF, München, Germany.
Int J Cancer. 2001 Sep;93(6):810-6. doi: 10.1002/ijc.1404.
Epstein-Barr virus (EBV) immortalized cells and Burkitt lymphoma cells have a completely different growth pattern and phenotype. EBV immortalized cells express a set of 11 viral genes to accommodate B cell activation and proliferation, whereas EBV-positive Burkitt lymphoma cells highly express the c-myc oncogene that is activated through translocation into 1 of the immunoglobulin loci and EBNA1 as the only viral protein. We have developed a primary human B cell line conditionally immortalized by Epstein-Barr virus in which the viral gene program responsible for the induction of proliferation can be switched on and off by the addition or withdrawal of estrogen (cell line EREB2-5). Starting from this cell line we have generated 2 daughter cell lines that proliferate in a c-myc dependent fashion, 1 with a highly active exogenous c-myc gene (cell line A1) and 1 with a regulatable c-myc gene that can be switched on by withdrawal and switched off by addition of tetracycline (cell line P493-6). The comparison of the 3 cell lines has allowed us to dissect the contribution of c-myc and EBV genes to the regulation of the growth pattern and expression of cell surface molecules. We show that MYC and EBNA2 (and their respective target genes) have opposing effects on the expression of several surface markers involved in B cell activation. We show that MYC contributes to the phenotype of Burkitt lymphoma cells by upregulating CD10 and CD38 and downregulating activation markers. The phenotype of the cells is determined on one hand by the absence of the viral gene products EBNA2 and LMP1 that mediate the phenotype of activated lymphoblasts and to a lesser extent by an active contribution of the c-myc gene.
爱泼斯坦-巴尔病毒（EBV）永生化细胞和伯基特淋巴瘤细胞具有完全不同的生长模式和表型。EBV永生化细胞表达一组11个病毒基因以适应B细胞的激活和增殖，而EBV阳性伯基特淋巴瘤细胞则高表达c-myc癌基因，该基因通过易位至免疫球蛋白基因座之一而被激活，并且EBNA1是唯一的病毒蛋白。我们开发了一种由爱泼斯坦-巴尔病毒条件性永生化的原代人B细胞系，其中负责诱导增殖的病毒基因程序可通过添加或去除雌激素来开启或关闭（细胞系EREB2-5）。从该细胞系出发，我们产生了2个子代细胞系，它们以c-myc依赖的方式增殖，1个带有高活性的外源性c-myc基因（细胞系A1），另1个带有可调节的c-myc基因，该基因可通过去除四环素开启并通过添加四环素关闭（细胞系P493-6）。对这3个细胞系的比较使我们能够剖析c-myc和EBV基因对生长模式调节和细胞表面分子表达的贡献。我们表明，MYC和EBNA2（及其各自靶基因）对参与B细胞激活的几种表面标志物的表达具有相反的作用。我们表明，MYC通过上调CD10和CD38并下调激活标志物来促成伯基特淋巴瘤细胞的表型。细胞的表型一方面由介导活化淋巴母细胞表型的病毒基因产物EBNA2和LMP1的缺失所决定，另一方面在较小程度上由c-myc基因的积极作用所决定。
