Project description:Whether the human tumor virus, Epstein-Barr virus (EBV) promotes breast cancers remains controversial and a potential mechanism has remained elusive. Here we show EBV can infect primary mammary epithelial cells (MECs) that express the attachment receptor, CD21. EBV infection leads to the expansion of early MEC progenitor cells with a stem cell phenotype and enforces a differentiation block. When MECs were implanted as xenografts, EBV infection cooperated with activated Ras and accelerated the formation of breast cancer. Infection in EBV-related tumors was of a latency type II pattern, including expression of latent membrane proteins 1 (LMP1) and 2 (LMP2), similar to nasopharyngeal carcinoma (NPC). A human gene expression signature for EBVness was generated based on the RNA expression profile of the EBV infected primary mammary epithelial cells, tumors. This was signature associated with high grade (40 vs 13.5%) estrogen-receptor-negative status (31.8 vs. 10.5%, p53 mutation (37.5 vs 14.5%) and poor survival. In 11/33 (33%) of tumors positive for EBVness EBV-DNA was found in tumor cells by fluorescent in situ hybridization for the viral LMP1 and BXLF2 genes, while only 4/36 (11%) of EBVness-negative tumors tested positive for EBV DNA. An analysis of the TCGA breast cancer data revealed a correlation of EBVness with presence of the APOBEC mutational signatures consistent with past viral infection. We conclude that a contribution of EBV to breast cancer etiology via a ‘hit-and-run’ mechanism is plausible, in which EBV infection predisposes mammary epithelial cells to malignant transformation, but is not required for the maintenance of the malignant phenotype.
Project description:RATIONALE: The Epstein Barr virus can cause cancer and lymphoproliferative disorders. Ganciclovir is an antiviral drug that acts against the Epstein Barr virus. Arginine butyrate may make virus cells more sensitive to ganciclovir. Combining ganciclovir and arginine butyrate may kill more Epstein Barr virus cells and tumor cells.
PURPOSE: Phase I trial to study the effectiveness of arginine butyrate plus ganciclovir in treating patients who have cancer or lymphoproliferative disorders that are associated with the Epstein Barr virus.
Project description:Gene expression profile of AGS gastric carcinoma cell line infected in vitro with Epstein-Barr Virus. Some samples also contain are stably transfected with a dominant negative LMP1 construct.
Project description:Epstein-Barr virus is associated with several human malignancies, including Burkitt Lymnphoma. The virus encodes more than 40 microRNAs, which participate in its possible pathogenetic role. We used microarrays to study the effect of the expression of an Epstein-Barr virus-encoded microRNA (ebv-BART6-3p) on the global gene expression profile of Burkitt Lymphoma cell lines.
Project description:Gene expression profile of AGS gastric carcinoma cell line infected in vitro with Epstein-Barr Virus. Some samples also contain are stably transfected with a dominant negative LMP1 construct. 8 total samples. 4 biological replicates of EBV infected cells, 2 biological replicates with EBV infected cells with LMP1DN construct, and 2 biological replicates with EBV infected cells with control vector.
Project description:Epstein-Barr virus has been reported to regulate cellular microRNA expression in B cells. In the present study, we investigated the differential microRNAs modulated by Epstein-Barr virus in Naspharyngeal Carcinoma, using CapitalBio corporation's mammalian miRNA arrays. Three cellular models were used in this study: the human naspharyngeal carcinoma cell line TW03 as a blank control; TW03 transfected with Epstein-Barr virus encoded LMP1; TW03 transfected with Epstein-Barr virus encoded LMP2A
