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1999 Fiscal Year Final Research Report Summary

Isolation of the genes involved in the process of differentiation inhibition and apoptosis induced by PU.1 in murine erythroleukemia cells

Research Project

Project/Area Number 10670977
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionSasaki Institute

Principal Investigator

YAMADA Toshiyuki  Sasaki Institute, Dept. of Cell Genetics, Chief Research Fellow, 細胞遺伝部, 主任研究員 (20183981)

Co-Investigator(Kenkyū-buntansha) YONEYAMA Hitomi  Sasaki Institute, Dept. of Cell Genetics, Research Fellow, 細胞遺伝部, 研究員 (30290977)
NEGISHI Fumiko  Sasaki Institute, Dept. of Cell Genetics, Research Fellow, 細胞遺伝部, 研究員 (40177902)
Project Period (FY) 1998 – 1999
KeywordsPU.1 / erythroleukemia / cell differentiation / apoptosis / Differential Display
Research Abstract

PU.1 is a transcription factor essential for development of myelomonocytes and B cells. In murine erythroleukemia (MEL) cells, PU.1 is expressed as the result of degenerated activation of the PU.1 gene. We previously showed that overexpression of PU.1 in MEL cells in the presence of differentiation-inducing reagent, DMSO, results in apoptosis but not differentiation of the cells. In the present study, by using the differential display strategy, we isolated 100 of known and 151 of unknown genes whose expression is changed in the process of PU.1-mediated differentiation inhibition and apoptosis in MEL cells.
The category of genes whose expression is up-regulated included some genes known to be implicated in regulation of cell cycle and/or cell proliferation and to be expressed normally in myelomonocyte- and B cell-lineage. The category of genes whose expression is down-regulated included some genes known to be important for function of mitochondria and ribosome and to be implicated in differentiation and survival of neural cells. It was also found that expression of a wide variety of myelomonocyte- and B cell-specific genes other than identified by differential display was up-regulated. Moreover, the cells became adherent and phagocytic after overexpression of PU.1, and the apoptosis was avoided, if not completely, by addition of myeloid growth factors such as GM-CSC and M-CSF to the culture. In addition, we are now trying to isolate the full length cDNA of the unknown genes identified.
Taken together, in this study, we identified some genes involved in differentiation inhibition and apoptosis in MEL cells and provided an evidence of lineage switching of MEL cells by PU.1 which might be one of the reasons for differentiation inhibition of the cells.

  • Research Products

    (12 results)

All Other

All Publications (12 results)

  • [Publications] F. Kihara-Nigishi et al.: "Down-regulation of c-Myc and Bcl-2 gene expression in PU.1-inducced apoptosis in murine erythrolekamia cells"International Journal of Cancer. 76. 523-530 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] N. Kondoh,et al.: "Enhanced expression of the urokinase-type plasminogen activator gene and reducede colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells"British Journal of Cancer. 78. 718-723 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Yamada et al.: "Reducation of DNA binding activity of the GATA-1 transcription factor in the apoptotic process induced by overexpression of PU.1 in murine erythrolekamia cells"Experimantal Cell Research. 245. 186-194 (1998)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] H. Yamamoto, et al.: "Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP"Oncigene. 18. 1495-1501 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] T. Oikawa, et al.: "The role of Ets family transcription factor PU.1 in hematopoetic cell differentiation, proliferation and apoptosis"Cell Death and Differentiation. 6. 599-608 (1999)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] 山田俊幸、及川恒之: "Ets ファミリー転写因子PU.1と血球分化"分子細胞治療. 1. 166-171 (2000)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] F.Kihara-Negishi, et al.: "Down-regulation of c-Myc and Bcl-2 gene expression in PU.1-induced apoptosis in murine erythroleukemia cells"Int. J. Cancer. 76. 523-530 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] N.Kondoh, et al.: "Enhanced expression of the urokinase-type plasminogen activator gene and reducede colony formation in soft agar by ectopic expression of PU.1 in HT1080 human fibrosarcoma cells"Br. J. Cancer. 78. 718-723 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Yamada et al.: "Reduction of DNA binding activity of the GATA-1 transcription factor in the apoptotic process induced by overexpression of PU.1 in murine erythroleukemia cells"Exp. Cell Res.. 245. 186-194 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] H.Yamamoto, et al.: "Physical and functional interactions between the transcription factor PU.1 and the coactivator CBP"Oncigene. 18. 1495-1501 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Oikawa, et al.: "The role of Ets family transcription factor PU.1 in hematopoietic cell differentiation, proliferation and apoptosis"Cell Death and Diff.. 6. 599-608 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] T.Yamada, et al.: "Ets family transcription factor PU.1 and hematopoiesis (in Japanese)"Bunshi-saibo-chiryo. 1. 166-171 (2000)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2001-10-23  

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