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Autocrine Proliferation and Differentiation-Capacities of Leukemic Cells, and Molecular Analyses of Leukemic Phenotypes

Research Project

Project/Area Number 62480263
Research Category

Grant-in-Aid for General Scientific Research (B)

Allocation TypeSingle-year Grants
Research Field Hematology
Research InstitutionJichi Medical School

Principal Investigator

SAITO Masaki  Jichi Medical School, Professor, 医学部, 教授 (60012762)

Co-Investigator(Kenkyū-buntansha) MOTOYOSHI Kazuo  Jichi Medical School, Associate Professor, 医学部, 助教授 (80137702)
NAKAMURA Mitsuru  Jichi Medical School, Associate, 医学部, 助手 (20198237)
FURUKAWA Yusuke  Jichi Medical School, Associate, 医学部, 助手 (00199431)
OHTA Masatsugu  Jichi Medical School, Lecturer, 医学部, 講師 (90160514)
KITAGAWA Sei-ichi  Jichi Medical School, Lecturer, 医学部, 講師 (50133278)
須田 年生  自治医科大学, 医学部, 講師 (60118453)
野尻 久雄  自治医科大学, 医学部, 助手 (70180742)
Project Period (FY) 1987 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥6,000,000 (Direct Cost: ¥6,000,000)
Fiscal Year 1988: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1987: ¥5,000,000 (Direct Cost: ¥5,000,000)
Keywordsgene transfection / malignant phenotype / tumorigenicity / autocrine growth / electroporation / FCC-P2 / NFS-60 / エレクトロポレーション / インターロイキン3 / 無制限増殖能
Research Abstract

Normal hemopoietic progenitors proliferate and differentiate to produce mature functioning cells, depending on a variety of hemopoietic growth factors, of which genes have been recently cloned. In contrast, autocrine growth mechanism(s) have been proposed especially at the onset of leukemia, a type of hemopoietic malignancy, since leukemia have been considered to develop from the transformation and clonal proliferation of hemopoietic precursors. The concept of autocrine mechanism(s) of cellular proliferation suggests that a cell can both produce and respond to a particular growth factor. Then, under certain conditions, such a cell might become independent of external growth regulation in a manner that would lead to malignant transformation. In order to elucidate the mechanism of malignant transformation of hemopoietic cells, we investigated the tumorigenicity of FDC-P2, an IL-3-dependent murine myeloblastic cell line established from a long-term culture of normal bone marrow cells, aft … More er transfection of the cDNA encoding murine IL-3 by electroporation. Two sublines growing in the absence of growth factors were established. Southern blot analysis using the probe of IL-3 gene showed that one cell line contained one copy of the integrated IL-3 gene, and the other contained 2-3 copies. A significant amount of IL-3 was detected in cutured media of these cell lines. These results suggest that the expression of IL-3 gene and the secretion of IL-3 transformed IL-3-dependent cells to IL-3-independent cells. Subcutaneous transfer of these cells into nude mice consistently produced tumors. The capacity of the transfected cells producing IL-3 appeared to confer a tumorigenic phenotype to these cells. Similar results were obtained with another murine myelomonocytic cell line, NFS-60 cells. In the latter case, 10 clones which became independent of IL-3 were established after transfection with IL-3 gene into the parental IL-3-dependent cell line. The capacities to produce IL-3 outside the cell were varied with different clones. However, the IL-3 activity inside the cell was found not to be much less different among the clones. Thus, the intracellular IL-3 activity was considered to be crucial for the autocrine growth of the transformed cells produced by transfection of the growth factor gene. Less

Report

(3 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Furukawa,Y.;Ohta,M.;Kasahara,T.;Miura,Y.;Saito,M.: Cancer Res.47. 2589-2593 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Suda,J.;Eguchi,M.;Akiyama,Y.;Iwama,Y.;Furukawa,T.;Sato,Y.;Miura,Y.;Suda,T.;Saito,M.: Blood. 69. 508-512 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Naito,M.;Kudo,I.;Nakagawa,Y.;Waku,K.;Nojiri,H.;Saito,M.;K.Inoue: J.Biochem.102. 155-162 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nojiri;S.Kitagawa;M.Nakamura;K.Kirito;Y.Enomot;M.Saito: J.Biol.Chem.263(16). 7443-7446 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Akashi;F.Takaku;H.Nojiri;Y.Miura;Y.Nagai;M.Saito.: Blood. 72(2). 469-479 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] K.Hara;T.Suda;J.Suda;M.Eguchi;J.N.Ihle;S.Nagata;Y.Miura;M.Saito.: Exp.Hematol.16. 256-261 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 斎藤政樹: "Annual Review 血液 1988" 中外医学社, 18 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 斎藤政樹: "医科分子生物学" 南江堂, 12 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Furukawa; M.Ohta; Y.Miura; M.Saito: "Interleukin-1 Derived from Human Monocytic Leukemia Cell Line JOSK-I Acts as an Autocrine Growth Factor" Biochem.Biophys.Res.Commun.147. 39-46 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] K.Hara;T.Suda;J.Suda;M.Eguchi;J.N.Ihle;S.Nagata;Y.Miura;M.Saito.: "Bipotential Murine Hemopoietic Cell Line (NFS-60) That Is Responsive to IL-3, GM-CSF, G-CSF,and Erythropoietin" Exp.Hematol.16. 256-261 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] Y.Furukawa; M.Ohta; T.Kasahara; Y.Miura; M.Saito: "Constitutive Prodduction of Interlleukin 1 by Human Monocytic Leukemia Cell Line JOSK-I and the Production Mechanism" Cancer Res.47. 2589-2593 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nojiri; S.Kitagawa; M.Nakamura; K.Kirito; Y.Enomoto; M.Saito: "Neolacto-series Gangliosides Induce Granulocytic Differentiation of Human Promyelocytic Leukemia Cell Line HL-60" J.Biol.Chem.263. 7443-7446 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Akashi; F.Takaku; H.Nojiri; Y.Miura; Y.Nagai; M.Saito: "Neutral and Sialosyl Glycosphingolipid Composition and Metabolism of Human T-Lymphoblastic Cell Line MOLT-3 Cells: Dinstinctive Changes as Markers Specific for Their Differentiation" Blood. 72. 469-479 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] M.Saito: Biochemical Studies on Membranes of Leukemic Cells. Chugai Igakusha Co. LTD, 191-208 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] H.Nojiri,;S.Kitagawa,;M.Nakamura,;K.Kirito,;Y.Enomoto,;M.Saito.: J.Biol.Chem.263(16). 7443-7446 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] M.Akashi,;F.Takaku,;H.Nojiri,;V.Miura,;Y.Nagai,;M.Saito.: Bllod. 72(2). 469-479 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] K.Hara,;T.Suda,;J.Suda,;M.Eguchi,;N.Ihle,;S.Nagata,;Y.Miura,;M.Saito.: Exp.Hematol.16. 256-261 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Y.Sato,;K.Kitano,;S.Tsunoda,;M.Yoshida,;E.Kaji,;T.Suda,;S.Sakamoto,;K.Motoyoshi,;M.Saito,;Y.Miura.: Blood. 71(6). 1561-1567 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] A.Ohsaka,;M.Saito,;I.Suzuki,;Y.Miura,;F.Takaku,;S.Kitagawa.: Biochim.Biophys.Acta. 941. 19-30 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] M.Ohta,;F.Takaku,;Y.Miura,;S.Kitagawa,;M.Saito.: Jpn.J.Cancer Res.79. 350-358 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 斎藤政樹: "Annual Review 血液 1988 高久史磨、青木延雄、仁保善之、長尾大 編" 中外医学社、東京, 18 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 斎藤政樹: "がん・バイオサイエンスニュース 渋谷正史、吉田光昭 編" 「バイオサイエンスの進展に基づくがんの重点研究」総括班, 8 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] Furukawa.Y;Ohta.M;Kasahara.T;Miura.Y;and.Saito.M: Cancer Res. 47. 2589-2593 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Suda.J;Eguchi.M;Akiyama.Y;Iwama.Y;Furukawa.T;Sato.Y;Miura.Y;Suda.T;and.Saito.M: Blood. 69. 508-512 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Naito.M;Kudo.I;Nakagawa.Y;Waku.K;Nojiri.H;Saito.M;and.K.Inoue: J.Biochim. 102. 155-162 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Furukawa.Y;Ohta.M;Miura.Y;and.Saito.M: Biochem.Biophys.Res.Commun. 147. 39-46 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Furukawa.Y;Ohta.M;Miura.Y;and.Saito.M: Brit.J.Haematol. 65. 11-15 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Mori,M;Suda.T;Suda.J;Miura.Y;and.Saito.M: Acta Haematol.Jpn. 50. 59-64 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] 斎藤政樹;編集:高久史暦;青木延雄;仁保喜之;長尾大: "Annual Review 血液 1988" 中外医学社, 東京, 18 (1988)

    • Related Report
      1987 Annual Research Report
  • [Publications] 斎藤政樹;村松正実編集: "医科分子生物学" 南江堂, 東京, 12 (1987)

    • Related Report
      1987 Annual Research Report

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Published: 1987-04-01   Modified: 2016-04-21  

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