| Project/Area Number |
06670574
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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 | OSAKA CITY UNIVERSITY |
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Principal Investigator |
NISHIGUCHI Shuhei Osaka City Univ.Medical School, Assistant Professor, 医学部, 講師 (10192246)
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| Co-Investigator(Kenkyū-buntansha) |
TAKEDA Tadashi Osaka City Univ.Medical School, Assistant Professor, 医学部, 助手 (10254393)
NAKAJIMA Shinya Osaka City Univ.Medical School, Assistant Professor, 医学部, 講師 (50180287)
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| Project Period (FY) |
1994 – 1996
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| Project Status |
Completed (Fiscal Year 1996)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1996: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1995: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1994: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | hapatocellular carcinoma / representative difference analysis / comparative genomic hybridization / ornithine decarboxylase / interferon regulatory factor-1 / PEST region / hepatocellular carcinoma / 肝癌 / 遺伝子異常 / RDA / ODC / IRF-I / 肝細胞癌 / 癌遺伝子 / オルニチン脱炭酸酵素 / FISH |
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| Research Abstract |
During carcinogenesis leading to colon cancer, several genetic alternations accumulate. Vogelatein et al have postulated that such carcinogenesis necessarily involves several steps. In hapatocellular carcinoma, several genetic changes have been identified often in the genes c-myc, c-jun, and p53. That the incidence of these abnormalities in patients is generally low suggests that a more important genetic change in this tumor has probably not yet been identified. We set out to identified still unknown genetic alternations in hepatocellular carcinoma tissue by using representative difference analysis or comparative genomic hybridization. By these methods, we cloned several cDNAs detected in hepatocellular carcinoma tissue but not in liver tissues. The results of experiments were not reproducible. During the experiments, we confirmed certain genetic abnormalities in the ornithine decarboxylase (ODC) and interferon regulatory factor-1 (IRF-1) genes. The expression of mRNA coding for IRF-1 was greater in cancerous tissue, and there was exon skipping in the gene in such tissue. The ODC gene in advanced liver cancer have point mutations that affected the PEST region of the protein. We expressed an ODC clone that had a mutation in PEST region in a reticulocyte lysate ; the half-life of the mutant enzyme protein was prolonged, and its activity was increased compared with wild-type ODC.
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