| Summary: | 碩士 === 慈濟大學 === 生命科學研究所 === 96 === Prostate apoptosis respopnse-4 (Par-4) is a pro-apoptotic protein. Various apoptotic insults resulted in elevated expression of Par-4, or ectopically over-expression of Par-4, can selectively sensitize tumor cells to apoptosis. Our previous study showed that Par-4 expression was abundant in tumor part of nasopharyngeal carcinoma (NPC) biopsies in contrast to normal nasoepithelium. Latent membrane protein 1(LMP1) is important viral oncoprotein of EBV and associated with NPC tumorgenesis. In the present study, we demonstrated that protein expression and stability of Par-4 were apparently diminished by LMP1 but unrelated with par-4 transcription. Meanwhile, by using PI3K inhibitor LY294002, dominant negative Akt, respectively, the pro-apoptotic ability of Par-4 through phosphorylation by PKA was further repressed by LMP-1 via PI3K/Akt signaling pathway. However, we discovered that PKA and phospho-PKA protein expression were induced by LMP1. To protect cell form apoptosis, we also demonstrated LMP1 induced Bcl-2 expression through NF-κB pathway to inhibit the pro-apoptotic ability of Par-4. In conclusion, our data provide new evidence that LMP-1 could participate in NPC tumorgenesis via down-regulated Par-4 expression and activity.
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