Overview

This dissertation, Functional Studies of Epstein-Barr Virus Latent Membrane Protein 1 in Nasopharyngeal Epithelial Cells by Hoi-ming, Li, 李海明, was obtained from The University of Hong Kong (Pokfulam, Hong Kong) and is being sold pursuant to Creative Commons: Attribution 3.0 Hong Kong License. The content of this dissertation has not been altered in any way. We have altered the formatting in order to facilitate the ease of printing and reading of the dissertation. All rights not granted by the above license are retained by the author. Abstract: Abstract of thesis entitled Functional studies of Epstein-Barr Virus Latent Membrane Protein_1 in nasopharyngeal epithelial cells Submitted by Li, Hoi Ming for the degree of Doctor of Philosophy at The University of Hong Kong on 31 March 2004 Nasopharyngeal carcinoma (NPC) is a common disease in Hong Kong and Southern provinces of China. The incidence rate of NPC could reach to 25-50 per 100,000 per year. NPC is closely associated with Epstein-Barr virus (EBV) infection. Over 95% of the world's population carries latently infected EBV in their B cells. EBV genome could be detected in most of the NPC cells. Role of EBV in the pathogenesis of NPC is largely unknown. Understanding the mechanisms of tumorigenesis by EBV is essential for better prevention and treatment of NPC. Previous studies have found that several of the EBV latent genes modulate cellular phenotype and growth characteristics, in which the oncogene Latent Membrane Protein 1 (LMP1) is believed to play important role in malignant transformation. The main focus of my research is on the mechanisms of LMP1 in transformation of nasopharyngeal epithelial cells. In this study, a novel function of LMP1 to induce Id1 expression in nasopharyngeal epithelial cells (NP69) and INK4a HEK293 is reported. Id1 is a negative transcriptional regulator of p16 . Expression of Id1 facilitates cellular immortalization and stimulates cell proliferation. With the combination of both specific chemical and genetic inhibitors of cell signaling, induction of Id1 by LMP1 was shown to be dependent on its NF-κB activation domain at the carboxy-terminal region, CTAR1 and CTAR2. Induction of Id1 by LMP1 may facilitate clonal expansion of premalignant nasopharyngeal epithelial cells infected with EBV and may promote their malignant transformation. Previous studies have shown that LMP1 activates Cdc42, which mediate some phenotypic changes such as actin reorganization. Such changes are known to relate to cell cycle progression, cytokinesis and adhesion, which are involved in carcinogenesis. LMP1 was shown to be able to activate Cdc42 in 3T3 fibroblasts. Here Cdc42 was found to be activated by LMP1 in HEK293 and nasopharyngeal carcinomatoid SUNE1. This supports a role of LMP1 in carcinogenesis through constitutive activation of Cdc42 in nasopharyngeal epithelial cells. Previous studies have also shown that loss or alteration of E-cadherin occurs frequently in many different epithelial cancers. It has also been found to be downregulated in NPC. E-cadherin is a plasma membrane protein that functions in cell-cell adhesion. In my study, E-cadherin was found to be downregulated by LMP1 in nasopharyngeal carcinomatoid CNE2 and SUNE1. In NPC cells, inhibition of its expression was not related to the CTAR2 domain of LMP1. Currently, most of the functional studies on the transformation ability of EBV were demonstrated in either non-nasopharyngeal epithelial or transformed cell lines, which have aberrant cellular signaling systems that complicate the experiments. Hence, in this study, a near normal human nasopharyngeal epithelial cell line (NP460 hTert) has been established with the assistance of constitutive telomerase expression. The immortalized telomerase expressing cells have up-regulation in Id1, increased phosphorylation of IκBα, undetectable INK4a p16

Full Product Details

9781374710689

Table of Contents

Reviews

Author Information

Tab Content 6

Customer Reviews

Recent Reviews

Countries Available