1994 Fiscal Year Final Research Report Summary
Cloning of suppressor gene of metastasis using subtraction hybridization method
| Project/Area Number |
05671026
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
General surgery
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| Research Institution | Keio University |
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Principal Investigator |
KUBOTA Tetsuro Keio Univ., Dept.Surg., Assistant, 医学部, 助手 (00118944)
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| Project Period (FY) |
1993 – 1994
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| Keywords | Subtraction / HFREP-1 / Hepatocellular carcinoma / Fibrinogen |
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| Research Abstract |
A gene (HFREP-1) that is overexpressed in hepatocellular carcinomas (HCCs) has been identified using a subtractive and differential cDNA cloning approach. We isolated the gene from a lambdagt10 cDNA library that was constructed from the poly(A)+-enriched RNA of a HCC specimen. The expression patterns observed in HCCs from 20 patients were classified into three types ; HFREP-1 was overexpressed in HCCs compared with non-tumorous regions (NTRs) in 55%, expressed weakly in both regions (15%) and strongly in both (30%). The largest cDNA insert contained 1231 base pairs coding 312 amino acids. The deduced protein sequence contained a hydrophobic leader peptide with a site for cleavage. The putative protein sequence showed strong homology with fibrinogen beta- and gamma- subunites and other fibrinogen-related proteins (FRPs), including four cysteine conserved residues. However, the HFREP-1 protein lacked a platelet-binding site, cross-linking region and thrombin-sensitive site, which are crucial for fibrin clot formation. The gene expression was studied in various organs in the rat and was specific to the liver, but little or none was detected in the fetal rat liver. Of the human carcinoma cell lines investigated, HFREP-1 was detected only in the HCC cell lines. We suggest that the HFREP-1 gene is a new member of the family of fibrinogens and has different features from other known FRPs and its expression is regulated oncodevelopmentally in hepatocytes.
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[Publications] Furukawa, T., Kubota, T., Watanabe, M., Kuo, T., Kase, S., Saikawa, Y., Tanino, H., Teramoto, T., Ishibiki, K., Kitajima, M.and Hoffman, R.M.: "Immunochemotherapy prevents human colon cancer metastasis after orthotopic onplantation of histologically-intact tumor tissue in nude mice." Anticancer Research. 13. 287-292 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Kuo, T., Kubota, T., Watanabe, M., Furukawa, T., Teramonot, T., Ishibiki, K., Kitajima, M.and Hoffman, R.M.: "Early resection of primary orthotopically-growing human colon tumor in nude mouse prevents liver metastasis : Further evidence for patient-like hematogenous metastatic route." Anticancer Research. 13. 293-298 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Furukawa, T., Kubota, T., Watanabe, M., Kuo, T., Kitajima, M.and Hoffman, R.M.: "Differential chemosensitivity of local and metastatic human gastric cancer after orthotopic transplantation of histologically intact tumor tissue in nude mice." International Journal of Cancer. 54. 397-401 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Kuo, T., Kuobta, T., Watanabe, M., Furukawa, T., Kase, S., Tanino, H., Saikawa, Y., Ishibiki, K., Kitajima, M.and Hoffman, R.M.: "Site-specific chemosensitivity of human small-cell lung carcinoma growing orthotopically compared to subcutaneously in SCID mice : The importance of orthotopic models to obtain relevant drug evaluation data." Anticancer Research. 13. 627-630 (1993)
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「研究成果報告書概要(欧文)」より
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[Publications] Kubota, T., Kumai, K., Kitajima, M., Fujisaki, M., Yamada, Y., Ushijima, Y., Ishibiki, K.and Abe, O.: "Dose intensity of mitomycin C in adjuvant cancer chemotherapy for patients with gastri cancer." Journal of Surgical Oncology. 57 (1). 40-45 (1994)
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「研究成果報告書概要(欧文)」より
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