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Effects of cdc2 gene and EMC tenasc in on regulation of growth and differentiation of hematopoietic cells

Research Project

Project/Area Number 04454575
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, Professoor, 医学部, 教授 (60012762)

Co-Investigator(Kenkyū-buntansha) SAKAI Takao  Jichi Medical School, Associate, 医学部, 助手 (10235111)
FURUKAWA Yusuke  Jichi Medical School, Lecturer, 医学部, 講師 (00199431)
NAKAMURA Mitsuru  JIchi Medical School, Lecturer, 医学部, 講師 (20198237)
OHTA Masatsugu  jichi Medical School, Lecturer, 医学部, 講師 (90160514)
KITAGAWA Sei-ichi  Jichi Medical School, Assoc. Professoor, 医学部, 助教授 (50133278)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 1993: ¥1,700,000 (Direct Cost: ¥1,700,000)
Fiscal Year 1992: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsCell Cycle / cdc2 Gene Product / E2F Binding Site / Glycoprotein Tenascin / Extracellular Matrix / Nonepithelial Stroma Cells / Cell Growth Factors / Change Chromatin Structure / クロマチン構造変化 / 細胞外マトリックス / 非上皮系間質細胞 / 増殖因子 / (非)上皮系細胞
Research Abstract

Our recent research works brought about the following results : (1) Cdc2 mRNA transcript wasreadily detected in immature bone marrow cells and became undetectable accompanying with the cell cycle arrest which ocurred along wich differentiation : it was undetectable after the myelocyte/metamyelocyte stages in granulocytic differentiation. Peripheral blood resting cells including granulocytes, monocytes and T-lymphocytes did not express cdc2 mRNA transcripts. Cdc2 mRNA could be induced in T-lymphocytes when the cells re-entered the cell cycle in response to specific mitogens such as PHA.In contrast, cdc2 mRNA could not be induced in granulocytes and monocytes even after the culture with the appropriate stimulants such as LPS or CSFs. The changes in the chromatin structure such as the appearance of DNase I hypersensitivity sites or the slteration of DNA methylation status were not observed in T-lymphocytes even after the induction of cdc2 mRNA expression by mitogenic stimuli. Then, we isolated the regulatory sequence of cdc2 gene by a ligation-mediated PCR and found E2F binding site at the position of nt -117 to -124 and the RB control elements at the positions of nt -106 to -112 and -156 to -165. (2) Tenascin is a novel six-armed extracellular-matrix glycoprotein expressed in association with mesenchymal-epithelial interactions, and its expression is temporally restricted during oganogenesis and carcinogenesis. Immuoprecipitation studies revealed two ascites-hepatoma-derived cell lines and one sarcoma-derived line synthesized tenascin in vitro. The other cell lines examined, including all of those derived from normal hepatocytes, were negative for the expression of tenascin. Coculture studies were performed between epithelial and nonepithelial cell lines. No drastic change in tenascin expression was found after cocultuing the cells. As an in vivo study, cell lines were transplanted into nude mice. All xenografts of the epithelial lines were associated with a storong

Report

(3 results)
  • 1993 Annual Research Report   Final Research Report Summary
  • 1992 Annual Research Report
  • Research Products

    (30 results)

All Other

All Publications (30 results)

  • [Publications] M.Nakamura,A.Tsunoda,K.Sakoe,et al.: "Total Metabolic Flow of Glycosphingolipid Biosynthesis is Regulated by UDP-GlcNAc:Lactosylceramide β1→3N-Acetylglucosaminyltransferase and CMP-NeuAc:Lactosylcoramide α2→3Sialyltransferase in Human Hematopoictic Cell Line HL-60 During Differentiation." J.Biol.Chem.267. 23507-23514 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Y.Furukawa,S.Uenoyama,M.Ohta,et al: "Transforming Growth Factor-β(TGF-β) Inhibits Phosphorylation of the Retino-blastoma Susceptibility Gene Product in Human Monocytic Leukemia Cell Line JOSK-I." J.Biol.Chem.267. 17121-17127 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai,T.,Kawakatsu,H.,Hirota,N.,et al.: "Tenascin Expression in vitro and in vivo:Comparison between Epithelial and Nonepithelial Rat Cell Lines." Exp.Cell Res.206. 244-254 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yuo,A.,Kitagawa,S.,Azuma,E.,et al.: "Tyrosine phosphorylation and intracellular alkalinization are early events in human neutrophils stimulated by tumor necrosis factor,granulocyte-macrophage colony stimulating factor and granulocyte colony-stimulating factor." Biochim.Biophys.Acta. 1156. 197-203 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai,T.,Kawakatsu,H.,Hirota,N.,et al.: "Specific Expression of Tenascin in Human Colonic Neoplasms." Br.J.Cancer. 67. 1058-1064 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] E.K.Azuma,S.Kitagawa,A.Yuo,et al.: "Activation of the respiratory burst and tyrosine phosphorylation of proteins in human neutrophils:no direct relationship and involvement of protein kinase C-dependent and -independent signaling pathways." Biochim.Biophys.Acta. 1179. 213-223 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saito,Masaki: "Advances in Lipid Research,(edit.by R.M.Bell,A.H.Merril,and Y.A.Hannun)" Academic Press,New York, pp.303-327 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saito,Masaki: "Cancer Chemotherapy:Challenges for the Future,(edit.by Kimura,K.,Yamada,K.,Carter,S.K.,and Longo,D.L.)" Excerpta Medica,Ltd.Tokyo, pp.141-149 (1993)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai, T., Kawakatsu, H., Hirota, N., Yokoyama, T., Takaoka, T., Sakakura, T., and Saito, M.: "Tenascin Expression in vitro and in vivo : Comparison between Epithelial and Nonepithelial Rat Cell Lines." Exp. Cell Res.206. 244-254 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Yuo, A., Kitagawa, S., Azuma, E., Natori, Y., Togawa, A., Saito, M., and Takaku, F.: "Tyrosin phosphorylation and intracellular alkalinization are early events in human neutrophils atimulated by tumor necrosis factor, granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor." Biochim. Biophys. Acta. 206. 197-203 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai, T., Kawakatsu, H., Hirota, N., Yokoyama, T., Sakakura, T., and Saito, M.: "Specific Expression of Tenascin in Human Colonic Neoplasms." Br. J.Cancer. 67. 1058-1064 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] E.K.Azuma, S.KItagawa, A.Yuo, H.Mizoguchi, K.Umezawa, F.Takaku, and M.Saito: "Activation of the respiratory burst tyrosine phosphorylation of proteins in human neutrophils : no direct relationship and involvement of protein kinase C-dependent and -independent signaling pathways." Biochim. Biophys. Acta. 1179. 213-223 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Ohsaka, A., Kitagawa, S., Yuo, A., Motoyoshi, K., Furusawa, S., Miura, Y., Takaku, F., and Saito, M.: "Effects of granulocytes colony-stimulating factor and granulocyte-macrophhage colony-stimulating factor on respiratory burst activity of neutrophils in patients with myelodysplastic syndromes." Clin. Exp. Immunol.91. 308-313 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saito, Masaki: "Bioactive Gangliosides : Differentiation Inducers for Hematopoietic Cells and Their Mechanism(s) of Actions." Advances in Lipid Research, (edit., Merril, Bell, and Hannun) Academic Press, New York. Voi. 25. 303-327 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Saito, Masaki: "New differentiation inducers with reference to glycobiology : Bioactive glycolipids and mechanism(s) of their action" Cancer Chemotherapy : Challenges for the Future, (edit. by Kimura, K.et al.) Excerpta Medica, Ltd. Tokyo. Vol. 8. 141-149 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Sakai,T,,Kawakatsu,H.,Hirota,N.,et al.: "Tenascin Expression in vitro and in vivo:Comparison between Epithelial and Nonepithelial Rat Cell Lines." Exp.Cell Res.206. 244-254 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Yuo,A.,Kitagawa,S.,Azuma,E.,et al.: "Tyrosine phosphorylation and intracellular alkalinization are early events in human neutroprils stimulated by tumor necrosis factor.granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor." Biochim.Biophys.Acta. 1156. 197-203 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Sakai,T.,Kawakatsu,H.,Hirota,N.,et al.: "Specific Expression of Tenascin in Human Colonic Neoplasms." Br.J.Cancer. 67. 1058-1064 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] E.K.Azuma,S.Kitagawa.A.Yuo.et al.: "Activation of the respiratory burst and tyrosine phosphorylation of proteins in human neutrophils:no direct relationship and involvement of protein Kinase C-dependent and -independent signaling pathways." Biochim.Biophys.Acta. 1179. 213-223 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Ohsaka,A.,Kitagawa,S.,Yuo,A.,et al.: "Effects of granulocytes colony-stimulating factor and granulocyte-macrophage colony-stimulating factor on respiratory burst activity of neutrophils in patiecnts with myelodysplastic syndromes" Clin.Exp.lmmunol.91. 308-313 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saito,Masaki: "Academic Press,New York," Advances in Lipid Research,(edit.by R.M.Bel,A.H.Merril,and Y.A.Hannun). pp.303-327 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Saito,Masaki: "Excerpta Medica.Ltd.Tokyo," Cancer Chemotherapy:Challenges for the Future,(edit.by Kimura,K.,Yamada,K.,Carter,S,K.,and Longo,D.L.). pp.141-149 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] M.Nakamura,A.Tsunoda,K.Sakoe,J.Gu,A.Nishikawa,N.Taniguchi,and M.Saito,: "Total Metabolic Flow of Glycosphingolipid Biosynthesis is Regulated by UDP-G1cNAc:Lactosylceramide β1→3N-Acetylglucosaminyl-transferase and CMP-NeuAc:Lactosylceramide α2→3Sialyltransferase in Human Hematopoietic Cell Line HL-60 During Differentiation." J.Biol.Chem.267. 23507-23514 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Furukawa,S.Uenoyama,M.Ohta,A.Tsunoda,J.D.Griffin,and M.Saito: "Transforming Growth Factor-β(TGF-β) Inhibits Phosphorylation of the Retinoblastoma Susceptibility Gene Product in Human Monocytic Leukemia Cell Line JOSK-I." J.Biol.Chem.267. 17121-17127 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Yuo,S.Kitagawa,K.Motoyoshi,E.Azuma,M.Saito,and F.Takaku: "Rapid Priming of Human Monocytes by Human Hematopoietic Growth Factors:GM-CSF,M-CSF and IL-3 Selectively Enhance Superoxide Release Triggered by Receptor-Mediated Agonists" Blood. 79(6). 1553-1557 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Y.Ishida,Y.Furukawa,J.DeCaprio,M.Saito,and J.D.Griffin: "Treatment of myeloid leukemic cells with the phosphatase inhibitor okadaic acid induce cell cycle arrest at either G1/S or G2/M depending on dose." J.Cell.Physiol.150. 484-492 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] A.Ohsaka,S.Kitagawa,A.Yuo,K.Motoyoshi,M.Ohta,Y.Miura,F.Takaku,and M.Saito: "Increased Respiratory Burst Activity of Neutrophils in Patients with Aplastic Anemia:Effects of Granulocyte Colony-stimulating Factor and Granulocyte-Macrophage Colony-stimulating Factor" Exp.Hematol.20. 1090-1093 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] M.Katoh,T.Shirai,K.Shikoshi,M.Ishii,M.Saito,and S.Kitagawa: "Neutrophil kinetics shortly after initial administration of recombinant human granulocyte colony-stimulating factor:Neutrophil alkaline phosphatase activity as an endogenous marker." Eur.J.Haematol.49. 19-24 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Saito,Masaki: "Human Cell;Human Lymphocyte Culture:Perspective and Applications [Recent trends in research on differentiation of hematopoietic cells and lymphokines(hemopoietin)]" 蟹書房、東京, 16/85 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] 明石 真言、斎藤 政樹: "Annual Review 血液 1992(高久、青木、仁保、長尾編)[前骨髄球性白血病の分化誘導療法]" 中外医学社、東京, 8/259 (1992)

    • Related Report
      1992 Annual Research Report

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Published: 1992-04-01   Modified: 2016-04-21  

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