|Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
We have previously reported that expression of EB virus Latent Membrane Protein-1 (LMP 1) in Nasopharyngeal carcinoma (NPC) tissues correlates with invasiveness and malignancy. We succeeded in transformation of epithelial cell line from kidney, MDCK, as a model of malignant transformation of epithelial cells by LMP1. The transformed cells showed high invasive phenotype. We screened genes associated with invasiveness of the transformed cells, and found that a transcription factor Ets- 1 is up-regulated in these cells (Oncogene 30, 1764-1771, 2000). Expression of dominant negative form of Ets- 1 in the transformed reduced the invasive property. These results indicate that LMP1 induces invasive phenotype in epithelial cells by stimulating expression of Ets- 1. Next, we examined expression of genes in NPC tissues which could be regulated by Ets-1. Since we found that LMP1 expression correlates with angiogenesis, expression of genes associate with angiogenesis was examined. Interleukin-8 (IL8) expression was observed to be enhanced in NPC tissues expressing LMP1, and IL8 expression was demonstrated to be induced by LMP1 by an in vitro experiment (Clinical Cancer Res., 7, 1946-1951, 2001). Hepatocyte Growth Factor (HGF) is known to induce epithelial cell motility. We analyzed expression of the ligand of HGF (c-Met) in NPC. Expression of c-Met well correlated with the level of LMP1 in NPC, which could be demonstrated by an in vitro experiment (American Journal of Pathology, 159, 27-33). In this project we demonstrated that LMP1 is closely associated with the malignancy of NPC.