臺灣博碩士論文加值系統

Epstein-Barr virus (EBV) is a ubiquitous oncogenic γ-herpesvirus, that establishes both latent and lytic modes of infection in host cells, implicated to the etiologic agent of malignant disease in humans. Our early study suggested that EBV mediated transcription of Monocarboxylate Transporter 1 (MCT1) elicits downstream effects to negatively regulate the constitutive activation of LMP1 mediated NF-κB signalling, instead inducing a partial activation to prolong the EBV driven proliferation of lymphoblastoid cell lines (LCLs). In addition to their importance in EBV tumorigenesis, this study emphasizes MCT1 as a general requirement for the maintenance of cells derived from B lymphoma disorders. EBV infection in B cell in vitro induced MCT1 levels among MCT1-4, resulting in cytosolic localization. EBNA2 and EBNA3B preferentially activated MCT1 promoter-luciferase reporter activity. LMP1, in the presence of MCT1 was shown to partially stabilize the NF-κB inhibitor, IĸBα, promoting cell viability by reducing caspase 3 cleavage. Depletion of MCT1 using lentivirus-expressed short-hairpin RNAs (shRNAs) enhanced p65 nuclear localization by reducing IĸBα stabilization and consequently cell viability was vigorously impaired in EBV uninfected B lymphoma cells and EBV transformed LCLs. Taken together, our data provides a new insight to partly understand the importance for MCT1 requirement in B lymphoma disorders and the mechanism by which EBV exploits MCT1 to establish persistent B cell infection through down-regulation of NF-κB signalling.

Contents
Acknowledgements II
Abbreviations III
Abstract (English) IV
Introduction 1
Materials & Methods 5
Results 8
Discussion 14
Figures 17
References 26

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