EBV Conference 2008 Guangzhou - Baylor College of Medicine

141 (RegID: 1474; 1475)
chia-chun chen
Institution: Graduate Institute of Biomedical Sciences, Chang Gung University
e-mail: d9401210@stmail.cgu.edu.tw
THE EPSTEIN-BARR VIRUS ONCOGENE PRODUCT, LATENT MEMBRANE PROTEIN 1,
INDUCES EXPRESSION OF THYMIDINE PHOSPHORYLASE IN NASOPHARYNGEAL
CARCINOMA
Chia-chun Chen, Yu-Sun Chang
Posterabstract:
Thymidine phosphorylase (TP), which was firstly identified as an enzyme involved in reversible
conversion of thymidine to thymine and 2-deoxy-D-ribose-1-phosphate, also acts as an angiogenic and
anti-apoptotic factor contributing to tumor progression. Elevated TP expression is often detected in
various solid tumors, and considered as a tumor biomarker linked to poor prognosis. These phenomena
have also been verified in nasopharyngeal carcinoma (NPC) recently (Chen et al., 2008). However, the
molecular mechanisms underlying TP overexpression in tumors remain unclear. My present studies
demonstrated that both mRNA and protein levels of TP could be induced by an oncogenic protein, latent
membrane protein 1 (LMP1) encoded by EBV, which is closely associated with NPC. Transient
transfection studies indicated that both CTAR1 and CTAR2 domains of LMP1 C-terminus could mediate
TP induction based on the data using a series of LMP1 and LMP1 mutant constructs. Among specific
inhibitors for LMP1-mediated signaling pathways, the dose-dependent inhibition of BAY11-7082
indicated that the nuclear factor (NF)-κB, which is activated through both CTAR domains, was involved
in TP regulation. Furthermore, the ecotopically expressed p65 also upregulated the TP expression, and the
constitutively active form of IκB could abolish the LMP1-mediated TP induction. All these data
emphasized that the NF-κB signaling is important for TP regulation in nasopharyngeal carcinoma.
EBV Conference 2008 Guangzhou
- 205 -