| Summary: | 碩士 === 國立臺灣大學 === 微生物學研究所 === 96 === Epstein-Barr virus (EBV) is the etiologic agent of infectious mononucleosis and oral hairy leukoplakia. It is also associated with several human malignancies, such as Burkitt’s lymphoma, Hodgkin’s lymphoma and nasopharyngeal carcinoma (NPC), etc. NPC is a tumor derived from the epithelial cells of nasal-pharynx. Chromosomal instability has been demonstrated in the tumor cells by cytogenetic analysis. Chromosomal instability is highly associated with the development of cancer cells. Although the major viral products demonstrated in the NPC biopsy samples are derived from latent genes, many lytic gene products are also found in these samples. High antibody titers against viral lytic proteins can be detected in the serum samples obtained from NPC patients. These observations have led to the hypothesis that viral lytic replication is highly associated with the development of NPC. From our previous observation, the viral immediate-early protein Rta, the gene product of BRLF1 is able to interfere with the cell cycle progression and induce chromosomal instability. In this study we further demonstrate that Rta-induced micronucleus formation is mediated through the extracellular signal-regulated kinase (ERK) signaling pathway. In the presence of MEK1/2 inhibitor, U0126, the micronucleus formation ability is blocked. Enhanced ERK phosphorylation can be detected in cells expressing Rta protein. The kinase activity of the mitotic checkpoint protein, Aurora B kinase, is decreased and consequently leading to an early exist from the mitotic phase is demonstrated in Rta expressed cells.
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