Systematic Identification of Differentially Expressed and Methylation-Related Proteins in LMP-1-Expressing Cells and Nasopharyngeal Carcinoma (I)

Nasopharyngeal carcinoma (NPC) is a cancer notorious for its high metastatic ability and is closely associated with a human herpesvirus Epstein-Barr virus (EBV). EBV-encoded oncogene product LMP1 is expressed in NPC biopsies and can repress E-cadherin expression. The latter frequently occurs concomitantly with the acquisition of migration properties. We found that LMP1 can induce the DNA methyltransferase (DNMT) activity, resulting in the hypermethylation of the E-cadherin promoter (manuscript in preparation). In addition, DNMT exists as a phosphoprotein in vivo, and several kinase-mediated signal pathways are known to be activated by LMP1. However, the underlying mechanism is not clear. In order to understand the role of LMP1 in the metastasis of NPC, and to search for potential novel molecular markers, besides LMP1 (as the long-term goal), the specific aims of this three-year project are (1) to identify the DNMT-associated complexes induced by expression of LMP-1 (2) to identify the novel proteins differentially regulated by LMP-1-induced DNA methylation (3) to identify the cellular signaling pathway-associated protein kinases whose expression or phosphorylation status are altered in the presence of LMP1, and in response to the methylation inhibitor 5’-Aza-2’dC (4) to establish the global DNA methylation and protein phosphorylation pattern of LMP-1-expressing cells and clinical tissues This study should accomplish the following important missions: 1). The protein profiles of NPC tumor cells and NPC tumor cells that express LMP1 will be established; 2). The differentiated expressed or repressed proteins in the presence of LMP1 will be identified; 3). The proteins in the transcriptional repression complex induced by LMP1-mediated DNA methylation will be identified; 4). The target genes of LMP1-mediated DNA methylation will be identified; 5).The protein kinases that are involved in LMP1-mediated DNA methylation will be identified. This work will identify proteins, which are impor tant for cell transformation and metastasis. It will also provide the evidence for LMP1-induced epigenetic modification of tumor cells, which has never been explored before.

Project ID:PC9308-2402
External Project ID:NSC93-2745-B182-004-URD