Section of Pulmonary Diseases, Critical Care and Environmental Medicine, Department of Medicine, SL9, Tulane University School of Medicine, 1430 Tulane Avenue, New Orleans, LA 70112, USA.
Virol J. 2014 Jun 9;11:107. doi: 10.1186/1743-422X-11-107.
The Epstein-Barr virus (EBV) is a causal agent in a number of malignancies in humans including hematopoietic tumors and non-hematopoietic tumors. Burkitt's lymphoma cell lines containing the Epstein-Barr virus have been shown to form tumors in nude mice while clonal derivatives of such cell lines in which the viral genome has been lost do not (JID 177: 1194-1201, 1998; JV 72: 9150-9156, 1998; JV 68: 6069-6073, 1994). The re-introduction of EBV into these EBV negative BLs reconstitutes the tumor phenotype. Thus, EBV-induced cellular genes play critical role in EBV-related tumors.
In an attempt to identify cellular genes regulated by EBV that may contribute to its tumorigenic properties, we have enforced genome loss in the Burkitt's lymphoma (BL) line, MutuI, by introducing a dominant negative form of the episomal replication factor, EBNA1 and carried out gene array analysis. One of the genes identified by this analysis is PLAC1, a gene originally identified as being expressed exclusively in placental tissue. Real time RT-PCR analysis verified higher expression in EBV positive vs. EBV negative Mutu clones. Analysis of a panel of RNAs from 20 normal tissues demonstrated the highest level of expression in placenta but significant expression was also observed in testis and brain cerebellum. PLAC1 expression was also observed in non-BL tumor cell lines derived from breast, ovary, and prostate. Lastly, expression of PLAC1 was found to be higher in some primary breast tumors compared to normal adjacent tissues.
This data suggests that the EBV-induced PLAC1 is a member of the cancer/testis group of tumor antigens.
EB 病毒（EBV）是人类多种恶性肿瘤的致病因子，包括造血系统肿瘤和非造血系统肿瘤。含有 EBV 的伯基特淋巴瘤细胞系已被证明能在裸鼠中形成肿瘤，而失去病毒基因组的此类细胞系的克隆衍生物则不能（JID 177: 1194-1201, 1998; JV 72: 9150-9156, 1998; JV 68: 6069-6073, 1994）。将 EBV 重新引入这些 EBV 阴性 BL 中，可重建肿瘤表型。因此，EBV 诱导的细胞基因在 EBV 相关肿瘤中发挥关键作用。
为了鉴定可能有助于其致瘤特性的受 EBV 调节的细胞基因，我们通过引入潜伏膜蛋白 1 的显性负形式，在伯基特淋巴瘤（BL）细胞系 MutuI 中强制基因组缺失，并进行了基因阵列分析，从而尝试对 EBV 进行基因敲除。通过这种分析鉴定的一个基因是 PLAC1，这是一个最初被鉴定为仅在胎盘组织中表达的基因。实时 RT-PCR 分析证实，EBV 阳性 Mutu 克隆中的表达高于 EBV 阴性克隆。对来自 20 种正常组织的一组 RNA 的分析表明，该基因在胎盘组织中表达水平最高，但在睾丸和小脑组织中也有显著表达。PLAC1 表达也见于源自乳腺、卵巢和前列腺的非 BL 肿瘤细胞系。最后，发现一些原发性乳腺癌肿瘤组织中的 PLAC1 表达高于正常相邻组织。
这些数据表明，EBV 诱导的 PLAC1 是癌症/睾丸抗原这一肿瘤抗原家族的成员。
