| Summary: | 碩士 === 長榮大學 === 醫學研究所 === 94 === Epstein-Barr Virus (EBV) is a wide-spread human herpesvirus, which mainly infects human B-lymphocytes, T-lymphocytes and epithelial cells. EBV infection of B-lymphocytes resulting in B-lymphocyte transformation and immortalization and also induces the expression of eight latent proteins including six EBV nuclear antigens EBNA1, EBNA2, EBNA3A, EBNA3B, EBNA3C, EBNALP and three latent membrane proteins: LMP1, LMP2A and LMP2B.
Latent membrane protein 1(LMP1) is the most important oncoprotein expressed by EBV, which has been shown to be closely associated with Burkitt’s lymphoma, nasopharyngeal carcinoma, infectious mononucleosis, oral hairy leukoplakia, Hodgkin’s disease, T cell lymphoma and gastric carcinoma.
In order to understand the role of LMP1 in EBV-induced tumorigenesis, we started to investigate which genes are regulated by LMP1 in human epithelial cells. Previously we had established an LMP1-inducible RHEK cell line named RHEK-LMP1-(IND15) which can express LMP1 after doxycycline addition. We then compared the gene expression profile of cells with and without LMP1 expression by cDNA microarray analysis.
Our data showed that after doxycycline treatment 389 genes were up-regulation and 366 genes were down-regulation in a total of 7,684 cDNA clones. We then used real-time RT-PCR to analyse the expression level of 26 genes that are known to be involved in regulation of cell proliferation and migration. Among these genes, BMP-6 and MMP-19 were shown to be significantly upregulation after LMP1 induction. How these genes are upregulated were by LMP1 also investigated by the promoter-reporter assay. Our data indicated that LMP1 can only marginally activate BMP-6 and MMP-19 promoters. Since BMP-6 mRNA contains six AU-rich sequences in it’s 3’UTR, we also investigated whether LMP1 could induce the stabilization of BMP-6 mRNA. Our data indicated that LMP1 had no such ability.The mechanism by which LMP1 stimulate BMP-6 and MMP-19 expression needs further investigation.
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