| Co-Investigator(Kenkyū-buntansha) |
KUROSAKI Masayuki Tokyo Medical and Dental Univerity, Faculty of Medicine, Assistant, 医学部・附属病院, 助手 (10280976)
ENOMOTO Nobuyuki Tokyo Medical and Dental Univerity, Faculty of Medicine, Assoc.prof., 医学部・附属病院, 講師 (20251530)
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| Budget Amount *help |
¥8,800,000 (Direct Cost: ¥8,800,000)
Fiscal Year 2001: ¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 2000: ¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥4,100,000 (Direct Cost: ¥4,100,000)
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| Research Abstract |
To investigate oncogenes that are expressed specifically in hepatoma tissues and are responsible for hepatocarcinogenesis, the expression of genes were compared between hepatoma tissues and their surrrounding issues by a SSH method. Seven already-known genes were found to be overexposed and decorin to be underexpressed in hepatoma tissues. To investigate the role of HCV genome in hepatocarcinogenesis, HCV from patients with hepatoma and that from the others were compared. Certain mutations were observed more frequently in the former, and the number of the mutations was significantly increased. The heterogeneity of CD81, a putative odlular receptor for HCV, was not different between the patients with hepatoma and the others, while in the former, CD81 in the hepatoma and peripheral lymphocytes were different. Using a HCV replicon system, the NS5A protein was shown to trans-suppress the replication and a mutation in a serine residue in the upstream of the ISDR was critical for the replication. During the replication process, no remarkable changes were observed in the expression of 1217 genes by DNA microarray, but that of IL-8, GRO1, GRO2 was decreased. In tissues of chronic hepatitis, chemokine genes were over-expressed. In culture cells, the NS5A protein itself induced the expression of chemokine genes, which may be responsible for the pathogenesis of chronic hepatitis. In culture cells that expressed the core gene, the expression of v-myc, PCNA, DACD-1, and HDGF was increased, while that of v-jun, VEGF, IRF-1, and IL-8 was decreased. These changes may contribute hepatocarcinogenesis in chronic hepatitis C.
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