1993 Fiscal Year Final Research Report Summary
Effects of cdc2 gene and EMC tenasc in on regulation of growth and differentiation of hematopoietic cells
| Project/Area Number |
04454575
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
Hematology
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| Research Institution | Jichi Medical School |
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Principal Investigator |
SAITO Masaki Jichi Medical School, Professoor, 医学部, 教授 (60012762)
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| 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)
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| Project Period (FY) |
1992 – 1993
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| Keywords | Cell Cycle / cdc2 Gene Product / E2F Binding Site / Glycoprotein Tenascin / Extracellular Matrix / Nonepithelial Stroma Cells / Cell Growth Factors / Change Chromatin Structure |
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| 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
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[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)
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「研究成果報告書概要(和文)」より
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[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)
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[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)
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[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)
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[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)
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