• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

Role of the ret proto-oncogene in the development of the enteric nervous system

Research Project

Project/Area Number 06454192
Research Category

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

Allocation TypeSingle-year Grants
Research Field Experimental pathology
Research InstitutionNagoya University

Principal Investigator

TAKAHASHI Masahide  Nagoya University, School of Medicine, Department of Pathology, Associate Professor, 医学部, 助教授 (40183446)

Co-Investigator(Kenkyū-buntansha) WATANABE Yoshio  Nagoya University, School of Medicine, Department of Surgery, Assistant Professo, 医学部, 助手 (80201242)
Project Period (FY) 1994 – 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1995: ¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1994: ¥4,300,000 (Direct Cost: ¥4,300,000)
Keywordsret protooncogene / tyrosine kinase / Hirschsprung's disease / enteric neuron / Hirschosprung病 / 腸管神経系
Research Abstract

Immunohistochemical analysis with the anti-Ret antibody was performed to investigate the expression of the c-ret proto-oncogene product (c-Ret protein) in embryonic, and adult rat tissues. During embryogenesis, it was expressed at high levels in the enteric neuroblasts and the sympathetic ganglia. c-Ret positive cells appeared in the mesenchyme around the rofegut and the dorsal aorta at day 11.5 and formed the myeteric plexus of the whole embryonic gut and the sympathetic truck at later stages, respectively. In the enteric nervous system, c-Ret positive cells began to contact each other to form the myenteric ganglia and were arranged between the muscle layrs. After birth, these neurons continued to express the c-Ret protein at variable levels. These results suggested that the c-Ret protein might be involved in the development of the enteric and sympathetic nervous system.
We introduced several mutations of the ret proto-oncogene found in the Hirchsprung's disease.ret cDNA with each mutation was transfected into NIH 3T3 cells, cell lines expressing the mutant Ret proteins were established. The Ret proteins were usually expressed as a mature glycosylated form of 170 kDa protein present on the cell surface and an immature glycosylated form of the 150 kDa Ret protein in the endoplasmic reticulum. Western blot analysis revealed that very little of the 170 kDa Ret protein was expressed in transfectants while expression of the 150 kDa Ret protein was not affected. This result suggested that the Hirschsprung mutations impair the transport of the Ret protein to the plasma membrane.

Report

(3 results)
  • 1995 Annual Research Report   Final Research Report Summary
  • 1994 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Toyonori.Tsuzuki: "Spatial and temporal expression of the ret proto-oncogene product in embryonic,infant and adult rat tissues." Oncogene. 10. 191-198 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Naoya.Asai: "Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations." Mol.Cell.Biol.15. 1613-1619 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yoshio.Watanabe: "Expression of ret proto-oncogene products in the hypoganglionic segment of the small intestine of congenital aganglionosis rats." J.Pediatr.Surg.30. 641-645 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masahide.Takahashi: "Oncogenic activation of the ret proto-oncogene in thyroid cancer." Crit.Rev.in Oncogenesis. 6. 35-46 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] MasaKi.Wada: "Detection of Ret homodimers in MEN 2A-associated pheochromocytomas." Biochem.Biophys.Res.Commun.218. 606-609 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toshihide.Iwashita: "Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation." Oncogene. 12. 481-487 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tsuzuki, T., Takahashi, M., Asai, N., Iwashita, T., Matsuyama, M.and Asai, J.: "Spatial and temporal expression of the ret proto-oncogene product in embryonic, infant and adult rat tissues.19GC01 : Oncogene" 10. 191-198 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Asai, N., Iwashita, T., Matsuyama, M.and Takahashi, M.: "Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations." Mol.Cell Biol.15. 1613-1619 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Watanabe, Y., Ito, T., Harada, T., Takahashi, M., Kobayashi, S., Ozaki, T.and Nimura, Y.: "Expression of ret proto-oncogene products in the hypoganglionic segment of the small intestine of congenital aganglionosis rats." J.Pediatr.Surg.30. 641-645 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Takahashi, M.: "Oncogenic activation of the ret protooncogene in thyroid cancer" Crit.Rev.in Oncogenesis. 6. 35-46 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Wada, M., Asai, N., Tsuzuki, T., Maruyama, S., Ohiwa, M., Imai, T., Funahashi, H., Takagi, H.and Takahashi, M.: "Detection of Ret homodimers in MEN 2A-associated pheochromocytomas." Biochem.Biophys.Res.Commun.218. 606-609 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Iwashita, T., Asai, N., MuraKami, H., Matsuyama, M.and Takahashi, M.: "Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN2A or MEN2B mutation." Oncogene. 12. 481-487 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Toyonori Tsuzuki: "Spatial and temporal expression of the ret proto-oncogene product in embryonic,infant and adult rat tissues." Oncogene. 10. 191-198 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Naoya Asai: "Mechanism of acitvation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations." Mol.Cell.Biol.15. 1613-1619 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Yoshio Watanabe: "Expression of ret proto-oncogene products in the hypoganglionic segment of the small intestine of congenital aganglionosis rats." J.Pediatr.Surg.30. 641-645 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masahide Takahashi: "Oncogenic activation of the ret proto-oncogene in thyroid cancer." Crit.Rev.in Oncogenesis. 6. 35-46 (1995)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masaki Wada: "Detecion of Ret homodimers in MEN 2A-associated pheochromocytomas." Biochem.Biophys.Res.Commun.218. 606-609 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshihide Iwashita: "Identification of tyrosine residues that are essential for transforming activity of the ret proto-oncogene with MEN 2A or MEN 2B mutation." Oncogene. 12. 481-487 (1996)

    • Related Report
      1995 Annual Research Report
  • [Publications] Masahide Takahashi: "ret Proto-oncogene and human diseases" International Journal of Oncology. 4. 81-84 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Shoichi Maruyama: "Germ line mutations of the ret proto-oncogene in Japanese Patients with multiple endocrine neoplasia type 2A and type 2B" Japanese Journal of Cancer Research. 85. 879-882 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Dai Yan: "Recombinant ret oncogene products induce T lymphocyte Proliferation and suppress lymphoma derived from ret transgenic mice" International Journal of Oncology. 5. 661-665 (1994)

    • Related Report
      1994 Annual Research Report
  • [Publications] Toyonori Tsuzuki: "Spatial and temporal expression of the ret Proto-oncogene Products in embryonic,infant and adult rat tissues" Oncogene. 10. 191-198 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Naoya Asai: "Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations" Molecular and Cellular Biology. 15. 1613-1619 (1995)

    • Related Report
      1994 Annual Research Report
  • [Publications] Yoshio Watanabe: "Expression of ret Proto-oncogene Products in the hypoganglionic segment of the small intestine of congenital aganglionosis rats" Journal of Pediatric Surgery. (in press). (1995)

    • Related Report
      1994 Annual Research Report

URL: 

Published: 1994-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi