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IDENTIFICATION OF A TRANSCRIPTION-REGULATING FACTOR FOR NUCLEAR ONCOGENES AND ITS APPLICATION FOR DIAGNOSIS

Research Project

Project/Area Number 04670753
Research Category

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

Allocation TypeSingle-year Grants
Research Field General surgery
Research InstitutionTOHO UNIVERSITY

Principal Investigator

HEMMI Hiromichi  Toho University School of Medicine, Associate professor, 医学部, 助教授 (90165514)

Co-Investigator(Kenkyū-buntansha) TAKATSUKA Jun  Toho University School of Medicine, Associate professor, 医学部, 助教授 (30139026)
進藤 彦二  東邦大学, 医学部, 助手 (40235776)
Project Period (FY) 1992 – 1993
Project Status Completed (Fiscal Year 1993)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1993: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1992: ¥1,600,000 (Direct Cost: ¥1,600,000)
Keywordsmyc oncogenes / N-myc oncogene / transcription factor / transcription control region / 5'-flanking region / 発現制御領域 / 5′-flanking regin / 発現制御因子 / 5´-flanking region / BIAtore system / スクリーニング
Research Abstract

In this research porject, we studied the mechanism of expression of an oncogene family, mycs, especially N-myc. The regulatory mechanism of the myc gene transcription is unclear. The myc gene products (c-Myc, N-Myc, and L-Myc) forming hetrodimers with Max are known as transcription factors, though the target gene of the myc gene family are not known, yet. Gene amplification of the myc gene family is also known in certain malignant tumors. There is a correlation between the extent of the N-myc gene amplification and the malignancy in neuroblastoma, indicating that the measurement of the gene amplification potentially has a significance as a tumor maker.
In this study, to reveal the regulatory mechanism of N-myc oncogene expression, the transcription regulatory region located at 5'-flanking region of N-myc gene was first investigated. By 1992, N-myc gene including 5'-flanking region in TNB9 neuroblastoma cells of which N-myc gene is amplified was cloned and sequenced. In 1992 and 1993, to identify the control region, a reporter gene assay was carried out using the plasmids derived from N-myc gene of TNB9. Plasmids having CAT gene as a reporter gene and various length of 5'-flanking region, was newly constructed and studied the CAT activity in GOTO neuroblastoma cells as N-myc expressing cells and in HeLaS3 cells as N-myc non-expressing cells. The transcription-promoting and repressing regions were found in N-myc expressing cells and transcription-promoting regions were found in N-myc non-expressing cells. It is likely that there are more than one transcription factors regulating N-myc gene transcription in N-myc expressing cells. The cloning of the factor(s) and further investigation of abnormality of the factor(s) in various malignant tumor are neccessary.

Report

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

    (26 results)

All Other

All Publications (26 results)

  • [Publications] Shimatake,H.: "Storage form of N-myc oncoprotein in mammalian embryos." 小児がん. 29. 48-52 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Lie,B.: "Identification of the binding site of 55kDa tumor necrosis factor receptor by synthetic peptides." Biochem.Biophys.Res.Commun.188. 503-509 (1992)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 土田嘉昭: "小児がんの腫瘍マーカー" 癌の臨床. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shindo,H.: "Pleiotypic changes in expression of the N-myc gene in neuroblastoma cell lines treated with anti-cancer drugs." Recent Adv.Chem.Mol.Biol.Cancer Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimatake,H.: "Storage and Active forms of N-myc oncoprotein in mammalian embryos and their role in tumorigenesis and embryogenesis." Recent Adv.Chem.Mol.Biol.Cancer Res.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimatake,H.: "Hetrogeneous expression of N-myc Oncoprotein:Rolationship to cell cycle." Cliu.Chem.Eng.Commun. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimatake, H., Nakagawa, C., Hemmi, H., Inoue, A., and Makino.S.: "Storage form of N-myc oncoprotein in mammalian embryos." Jpn J Pediatr Oncol. 29. 48-52 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Lie, B., Tunemoto, D., Hemmi, H., Mizukami, Y., Fukuda, H., Kikuchi, H., Kato, S., and Numao N.: "Identification of the binding site of 55kDa tumor necrosis factor receptor by synthetic peptides." Biochem Biophys Res Commun. 188. 503-509 (1992)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Hemmi, H.: "Manual of selected cultured cell lines for biosicence and Biotechnology, Eds.K.Seno, H.Koyama, T.Toshio, Kyoritsu-Shuppan Co.Lts., Tokyo" HL-60. 6-7 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inoue, A, Hemmi, H., and Shimatake, H.: "The Basis for understanding the molecular biology of childhood tumors.Jpn J Pediatr Surg" 25. 828-835 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Inoue, A., Ihara.H., Kon, T., Nakamura.M., Suzuki, J., Aoki, T., Hemmi, H., and Shimatake, H.: "Polymorphism in the human dopamine D4 receptor (DRD4) gene in Japanese detected by PCR.Human Mol Genet" 2. 2197 (1993)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Tsuchida, Y., Yokomori, K., Taniguchi, F., Hemmi, H., Shimatake, H., Yamamoto, K., and Hanada, R.: "Tumor markers in childhood tumors." Gan-no-Rinsho. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shindo, H., Nakagawa, C., Hemmi, H., Ootsuka, S., and Shimatake, H.: "Pleiotypic changes in expression of the N-myc gene in neuroblastoma cell lines treated with anti-cancer drugs." Recent Advance in Chemistry and Molecular Biology of Cancer Research Springer-Verlag, Heidelberg.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimatake, H., Nakagawa, C., Tsukahara, T., and hemmi, H.: "Storage and active forms of N-myc oncoprotein in mammalian embryos and their role in tumorigenesis and embryogenesis" Recent Advance in Chemistry and Molecular Biology of Cancer Research.Springer-Verlag, Heidelberg.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] Shimatake, H., Shindo, H., Naruki, Y., Ohtsuka, S., Nakagawa, C., Hemmi, H.: "Heterogeneous expression of N-myc oncoprotein : Relationship to cell cycle." Clin Chem Enz Commun. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1993 Final Research Report Summary
  • [Publications] 逸見仁道: "分子生物学を理解するための基礎知識" 小児外科. 25. 828-835 (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hemmi,H.: "Pohymorphism in the humandopamine D4 receptorgene(DRD4)in Japanese" Human Mol.Genet.2. 2197- (1993)

    • Related Report
      1993 Annual Research Report
  • [Publications] Hemmi,H.: "Hetrogeneous Expression of N-mycoucoprotein;Relationship to Cell Cycle" Clin. Chem.Eng.Commun.in press

    • Related Report
      1993 Annual Research Report
  • [Publications] Hemmi,H.: "Pleiotypic Changes in expression of the N-myc gene in neuroblastoma cell lines" Recent Adv.chem.mol Biol.cancer Res.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] Hemmi,H.: "Storageand active forms of N-myc oncoprotein in mammalian embryos" Recent Adv,chem-mol.Biol.Cancer Res.(in press).

    • Related Report
      1993 Annual Research Report
  • [Publications] 逸見 仁道: "小児がんの腫瘍マーカー" 癌の臨床. (印刷中).

    • Related Report
      1993 Annual Research Report
  • [Publications] Hemmi , H.: "Storage form of N‐myc oncoprotein in mammaliun licrn embryos." 小児がん. 29. 48-52 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hemmi, H.: "Identification of the binding site of 55KDa tumerneciosis factor veceptor by synthetic peptides." Biochem. Biophys. Res. Commun.188. 503-509 (1992)

    • Related Report
      1992 Annual Research Report
  • [Publications] Hemmi, H.: "Pleiotypic changes in expression of the N‐myc gene in neuroblastomy cell lines treated with anti‐cancer diugs." Recent Adv. Chem. Mol. Biol. Cancer Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] Hemmi, H: "Storage and activeforms of N‐myconcopretein in mammaliun embryos and the in role in tumorigenesis and embryogenesis." Recent. Adv.Chem.Mol. Biol. Cancer Res.

    • Related Report
      1992 Annual Research Report
  • [Publications] Hemmi, H.: "Heterogeneous erpression of N‐myc oncoprotein: relationship to cell cycle" Clin. Chem. Eng. Commun.(1993)

    • Related Report
      1992 Annual Research Report

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

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