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Cloning and functional analysis of new oncogene in thyroid cancer

Research Project

Project/Area Number 13671158
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionNagasaki University

Principal Investigator

NANBA Hiroyuki  School of Medicine Associate Professor, 医学部, 助教授 (80237635)

Co-Investigator(Kenkyū-buntansha) TSUKAZAKI Tomoo  Graduate School of Biomedical Science A/Professor, 大学院・医歯薬学総合研究科, 助教授 (50315230)
YAMASHITA Shunichi  School of Medicine Professor, 医学部, 教授 (30200679)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsThyroid Cancer / Oncogene / Cloning
Research Abstract

To search new oncogenes in thyroid cancer, we performed cloning using new technique, which called smart method. The merit of this method is that very small amount of RNA (1μg) is good enough to make complete length cDNA. We constructed retroviral vector including cDNAs and transfeced to NIH3T3 cells. After 2 weeks of incubation, four colony piled up on the culture plate. When these transformed cells were subcutaneously injected to the nude mice, tumors developed within 2-3 weeks. We extracted DNA from the tumors and confirmed integration of human DNA by specific primers. Sequencing analysis revealed that one gene was truncated Raf-1 gene and other three were truncated BRAF gene. When these genes were transfected to the cells, we observed that the cells were transformed.
Next, we analyzed BRAF gene mutation using six human thyroid cancer cell lines and 186 thyroid tumor tissues. As the results, BRAF point mutation, V599E, was observed in four of six cell lines and 47 of 186 thyroid tumors. (25.3% ; 0/13 follicular adenoma, 0/7 follicular carcinoma, 45/160 papillary carcinomas and 2/6 undifferentiated carcinomas). Activation of MEK-MAP kinase pathway was observed in cell lines harboring BRAF mutation. BRAF mutation-associated enhanced cell growth was suppressed by MEK inhibitor, U0126. Examination of 135 patients with thyroid cancer showed that BRAF mutation correlated significantly with tumor size (P=0.015) and clinical stage (P=0.046). Our results indicate that activating mutation of BRAF gene could be a potentially useful marker of prognosis of patients with advanced thyroid cancers.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (13 results)

All Other

All Publications (13 results)

  • [Publications] N.Mitsutake, et al.: "PKC δ mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells"Oncogene. 20巻8号. 989-996 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saenko VA, et al.: "Problem of prevalence of ret/PTC rearrangements in thyroid tumors"Thyroid. 12巻5号. 435-436 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishigaki K, et al.: "Aberrant localization of beta-catenin correlates with overexpression of its target gene in human papillary thyroid cancer"J Clin Endocrinol Metab. 87巻7号. 3433-3440 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Furukawa K, et al.: "Functional domains of paired-like homeoprotein Cart1 and the relationship between dimerization and transcription activity"Genes Cells. 7巻11号. 1135-1147 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Mitsutake N, Namba H, Shklyaev SS, Tsukazaki T, Ohtsuru A, Ohba M, Kuroki T, Ayabe H, Yamashita S.: "PKC delta mediates ionizing radiation-induced activation of c-Jun NH(2)-terminal kinase through MKK7 in human thyroid cells"Oncogene. 22;20(8). 989-996 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Saenko VA, Rogounovitch TI, Abrosimov AY, Takamura N, Lushnikov EF, Namba H, Yamashita S.: "Problem of prevalence of ret/PTC rearrangements in thyroid tumors"Thyroid. 12(5). 435-436 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ishigaki K, Namba H, Takamura N, Saiwai H, Parshin V, Ohashi T, Kanematsu T, Yamashita S.: "Urinary iodine levels and thyroid diseases in children ; comparison between Nagasaki and Chernobyl"Endocr J.. 48(5). 591-595 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Furukawa K, Iioka T, Morishita M, Yamaguchi A, Shindo H, Namba H, Yamashita S, Tsukazaki T.: "Functional domains of paired-like homeoprotein Cart1 and the relationship between dimerization and transcription activity"Genes Cells. 7(11). 1135-1147 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] N.Mitsutake, et al.: "PKC δmediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells"Oncogene. 20巻8号. 989-996 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Saenko VA, et al.: "Problem of prevalence of ret/PTC rearrangements in thyroid tumors"Thyroid. 12巻5号. 435-436 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ishigaki K, et al.: "Aberrant localization of beta-catenin correlates with overexpression of its target gene in human papillary thyroid"J Clin Endocrinol Metab. 87巻7号. 3433-3440 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Furukawa K, et al.: "Functional domains of paired-like homeoprotein Cart1 and the relationship between dimerization and transcription activity"Genes Cells. 7巻11号. 1135-1147 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] N.Mitsutake, et al.: "PKC δ mediates ionizing radiation-induced activation of c-Jun NH2-terminal kinase through MKK7 in human thyroid cells"Oncogene. 20巻8号. 989-996 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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