| Project/Area Number |
10670211
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Experimental pathology
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| Research Institution | Nagasaki University School of Medicine |
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Principal Investigator |
SEKINE Ichiro Nagasaki University School of Medicine, Professor, 医学部, 教授 (60039922)
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| Co-Investigator(Kenkyū-buntansha) |
ITO Masahiro Nagasaki University School of Medicine, Associate Professor, 医学部, 助教授 (30184691)
NAKAO Kazuhiko Nagasaki University Health Center, Lecturer, 保健管理センター, 講師 (00264218)
OHTSURU Akira Nagasaki University School of Medicine, Assistant Professor, 医学部, 助手 (00233198)
MATSUYAMA Toshifumi Nagasaki University School of Medicine, Professor, 医学部, 教授 (30165922)
YAMASHITA Shunichi Nagasaki University School of Medicine, Professor, 医学部, 教授 (30200679)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Keywords | Hepatocellular carcinoma / Receptor-type tyrosine kinase / Oval cell / Preneoplastic lesic / Degenerated PCR |
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| Research Abstract |
BACKGROUND: Growth factor receptor tyrosine kinase signaling is known to play key roles in regulating growth and differentiation of normal hepatocytes, however, the specific receptor-type tyrosine kinases (RTKs) involved in hepatocarcinogenesis remain undetermined. AIMS: The aim of this study was to characterize the expression of these receptors in different stages of rat liver carcinogenesis, METHODS: We analyzed the expression profile of RTK genes in rat normal liver and diethylnitrosamine-induced hepatocellular carcinoma (HCC) tissues using a homology cloning method With degenerated primers. In situ hybridization, immunohistochemical staining, and RT-PCR were performed to analyze the cell type-specific expression of target RTKs during hepato-carcinogenesis. RESULTS: sequence analysis of 459 clones identified 23 different RTK genes. The Tie-2, c-Met, and Flk-1 genes were the most abundant RTKs expressed in rat HCC. Immunohistochemical and in situ hybridization studies showed overexpression of c-Met and Flk-1 in preneoplastic lesions as well as neoplastic lesions of HCC. Furthermore, Flk-1 mRNA expression was detected by RT-PCR in a hepatoma cell line of F344 rats. Tie-2 was expressed in endothelial cells of tumor vessels as well as in so-called oval cells, which are thought to be liver stem cells. CONCLUSION: Our results indicated the important role of c-Met, Tie-2 and VEGF/Flk-1 signals in different stages of hepatocarcinogenesis, suggesting specific and interdependent RTK expression during hepatocarcinogenesis.
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