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Function of parafibromin inhibiting parathyroid tumorigenesis

Research Project

Project/Area Number 17590963
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokushima

Principal Investigator

YOSHIMOTO Katsuhiko  The University of Tokushima Graduate School, Institute of Health Biosciences, Professor, 大学院ヘルスバイオサイエンス研究部, 教授 (90201863)

Co-Investigator(Kenkyū-buntansha) IWATA Takeo  The University of Tokushima Graduate School, Institute of Health Biosciences, Research Associate, 大学院ヘルスバイオサイエンス研究部, 助手 (10350399)
MIZUSAWA Noriko  The University of Tokushima Graduate School, Institute of Health Biosciences, Research Associate, 大学院ヘルスバイオサイエンス研究部, 助手 (80254746)
Project Period (FY) 2005 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 2005: ¥2,000,000 (Direct Cost: ¥2,000,000)
Keywordsparathyroid / hereditary tumor / endocrine / oncogene / tumor suppressor gene / 癌抑制遺伝子 / 癌 / 遺伝子
Research Abstract

Germline mutations of HRPT2 were found in 2 of 11 FIHP families and 1 of 2 HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas, and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in 2 of 5 parathyroid tumors in a family with 518-521 del mutation. Biallelic inactivation of HRPT2 by a combination of germline mutation and somatic mutation was confirmed in parathyroid tumors. The finding that 2 families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT.
Parafibromin is a 531-amino acid protein product encoded by HRPT2, a putative tumor suppressor gene recently implicated in the autosomal dominant hyperparathyroidism-jaw tumor familial cancer syndrome and sporadic parathyroid carcinoma. To investigate effects of parafibromin overexpression on cell proliferation, we performed cell proliferation assay in four different cell lines. Transient parafibromin overexpression inhibited cell growth in HEK293 and NIH3T3 cells, whereas enhanced cell growth in SV40 large T antigen expressing-cell lines such as 293FT and COS7 cells. In 293FT cells, the parafibromin was found to interact with SV40 large T antigen and overexpression of parafibromin promoted entry into S phase, implying that interaction between parafibromin and SV40 large T antigen enhanced cell cycle progression. Based on these we conclude that tumor suppressor protein, parafibromin, acts a positive regulator of cell growth such as oncoproteins at the presence of SV40 large T antigen.

Report

(3 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • Research Products

    (15 results)

All 2007 2006 Other

All Journal Article (15 results)

  • [Journal Article] A case of hyperparathyroidism-jaw tumour syndrome found in the treatment of an ossifying fibroma in the maxillary bone2007

    • Author(s)
      Yamashita Y et al.
    • Journal Title

      Int J Oral Maxillofac Surg 36(4)

      Pages: 365-369

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPAT1)2007

    • Author(s)
      Harada N et al.
    • Journal Title

      Mol Cell Biochem 297(1-2)

      Pages: 41-51

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas.2007

    • Author(s)
      Iwata T et al.
    • Journal Title

      Clinical Endocrinology 66(4)

      Pages: 499-502

    • NAID

      120005708873

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] A case of hyperparathyroidism-jaw tumor syndrome found in the treatment of an ossifying fibroma in the maxillary bone.2007

    • Author(s)
      Yamashita Y et al.
    • Journal Title

      Int J Oral Maxillofac Surg 36

      Pages: 365-369

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Molecular cloning of a murine glycerol-3-phosphate acyltransferase-like protein 1 (xGPATI)2007

    • Author(s)
      Harada N et al.
    • Journal Title

      Mol Cell Biochem 297

      Pages: 41-51

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] The aryl hydrocarbon receptor-interacting protein gene is rarely mutated in sporadic GH-secreting adenomas.2007

    • Author(s)
      Iwata T et al.
    • Journal Title

      Clinical Endocrinology 66

      Pages: 499-502

    • NAID

      120005708873

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Somatic mutations of the CTNNB1 gene in cribriform-morular variant of papillary thyroid carcinom2006

    • Author(s)
      Yoshimoto K et al.
    • Journal Title

      Recent Advances in Thyroid Cancer Research

      Pages: 93-103

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome2006

    • Author(s)
      Mizusawa N et al.
    • Journal Title

      Clinical Endocrinology 65

      Pages: 9-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Annual Research Report 2006 Final Research Report Summary
  • [Journal Article] Somatic mutations of the CTNNB1 gene in cribriform-morular variant of papillary thyroid carcinoma.2006

    • Author(s)
      Yoshimoto K et al.
    • Journal Title

      Recent Advances in Thyroid Cancer Research

      Pages: 93-103

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome.2006

    • Author(s)
      Mizusawa N et al.
    • Journal Title

      Clinical Endocrinology 65

      Pages: 9-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen

    • Author(s)
      Iwata T et al.
    • Journal Title

      Oncogene (In press)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen.

    • Author(s)
      Iwata T et al.
    • Journal Title

      Oncogene (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Parafibromin tumor suppressor enhances cell growth in the cells expressing SV40 large T antigen

    • Author(s)
      Iwata T et al.
    • Journal Title

      Oncogene (In press)

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Somatic mutations of the CTNNBI gene in cribriform-morular variant of papillary thyroid carcinoma

    • Author(s)
      Yoshimoto K et al.
    • Journal Title

      Recent Advances in Thyroid Cancer Research (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumor syndrome

    • Author(s)
      MizusSawa N et al.
    • Journal Title

      Clinical Endocrinology (In press)

    • Related Report
      2005 Annual Research Report

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Published: 2005-04-01   Modified: 2016-04-21  

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