Abstract
BackgroundThe 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.Methods and resultsIn 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.ConclusionThis data suggests that the EBV-induced PLAC1 is a member of the cancer/testis group of tumor antigens.
Highlights
The Epstein-Barr virus (EBV) is a causal agent in a number of malignancies in humans including hematopoietic tumors and non-hematopoietic tumors
Placental specific gene 1 (Plac1) is a member of a family of genes that have been identified as showing predominantly placenta specific gene expression [1,2,3,4,5] with expression being restricted to cells of trophoblastic lineage in the mouse and human [1,2]
Based on its expression profile and its localization to the X chromosome, we propose that PLAC1 is a candidate CT antigen
Summary
The Epstein-Barr virus (EBV) is a causal agent in a number of malignancies in humans including hematopoietic tumors and non-hematopoietic tumors. EBV-induced cellular genes play critical role in EBV-related tumors. Trophoblasts play numerous key roles in fetal development determined, in part, by differentiating along distinct pathways. These include the controlled invasion of extravillus trophoblasts into maternal uterine tissue resulting in placental attachment and regulatory interactions with the uterine vasculature. Multinucleated syncytiotrophoblasts are metabolically active cells that are in direct contact with the maternal circulation. They are responsible for many of the functions essential to pregnancy maintenance, i.e. nutrient and oxygen transport to the fetus, hormone production and secretion, and elimination of fetal waste products. The placenta contributes to immune tolerance necessary for effective placentation and pregnancy maintenance
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