1999 Fiscal Year Final Research Report Summary
STUDY FOR THE CELLULAR MECHANISMS OF INHIBITORY EFFECT OF THE TYPE I INTERFERON ON HEPATOCARCINOGENESIS AND CLINICAL APPLICATIONS
| Project/Area Number |
10670502
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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 |
Gastroenterology
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| Research Institution | Keio University |
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Principal Investigator |
SAITO hidetsugu Keio University, Internal Medicine, Assistant Professor, 医学部, 講師 (80186949)
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| Project Period (FY) |
1998 – 1999
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| Keywords | interferon / liver cancer cells / sensitivity to drugs / single nucleotide polymorphisms / promoter activity / signal transduction / interferon regulatory factor-1 / cell cycle |
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| Research Abstract |
The type I interferon (IFN) has been utilized in the treatment of chronic liver diseases caused by viral infection. We investigated the rate of occurrence of hepatocellular carcinoma (HCC) after the IFN-treatment for chronic hepatitis C, and the results suggested that IFN actively inhibited its occurrence rate. The precise mechanism of IFN-induced inhibition of hepatocarcinogenesis, however, has not been well understood. Therefore, we studied in vitro effect of IFN on the growth of HCC cell lines. IFN dose-dependently inhibited the growth of a group of cell lines, while there was another group of cells, in which IFN did not fully inhibit their proliferation. We then studied the difference of DNA and mRNA expression of interferon regulatory factors (IRF-1 and IRF-2), which is one of important signal transduction factors in IFN-induced transduction pathways, between the cell lines. The difference in the IRF-1 DNA rearrangement and the amount of IRF-1 mRNA were detected between two types of cell lines. We discovered the mutation in the intron 8 of the IRF-1 gene that causes DNA rearrangement when DNA was digested with BamHI. Genomic analysis of DNA from ten healthy volunteers revealed that this mutation seems to be a kind of single nucleotide polymorphisms (SNPs). We further investigated the difference in the IRF-1 promoter region that causes the difference in the IRF-1 mRNA amount. We discovered four SNPs in the upstream of the IRF-1 gene, which actually showed different promoter activities in luciferase reporter assay.
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