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Abnormalitis of growth signaling pathways in human thyroid cancer cells.

Research Project

Project/Area Number 11671097
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Endocrinology
Research InstitutionTokyo Woman's Medical University

Principal Investigator

TUSHIMA Toshio  Tokyo women's Mea univ. Dept. of Med. Professor, 医学部, 教授 (90101089)

Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2001: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2000: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
Keywordsthyroid cancer / MAPK / Akt / MEK / raf-1 / Bad / p70S6K / raf-1 / 甲状腺癌 / 乳頭癌 / 濾胞癌 / MAPキナーゼ
Research Abstract

Several abnormalities of oncogenes have been reported in human thyroid carcinomas. These abnormailites may be involved in molecular events leading to malignant transformation of thyroid carcinoma cells. However, a consistent or unifying pattern of activation of these protonogenes has not been seen, and there is no evidence that they are directly responsible for tumoregenesis. Clearly, events in addition to the activation of these cellular genes are important to the genesis of thyroid papillary carcinoma MAP kinase (MAPK) cascade (ras, rat-i, MEK and MAPK) and phosphoinositol 3 kinase (PI3K)-regulated kinases (PLB/Akt and p7OS6 kinase; p7OS6K) have been shown to play important roles in controlling cell proliferation. We attempted to determine if these pathways are dysregulated in human thyroid tumors. We found that both MAPK and MEK are overexpressed and constitutively activated compared to adjacent normal thyroid cells in a subset of papillary carcinomas and tollicular carcinomas. Expression of those kinases in follicular adenoma was much lower. Cancer cells also showed higher activities of p7OS6K and Akt. These findings suggest that these abnormalities are involved in uncontrolled growth of thyroid cell prolieration in a subset of thyroid cancers. Furthermore , inhibitors of the signaling pathway may be effective in treatment of thyroid cancer.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Tsushima T, Kato Y, Miyachi Y, Teramoto A, Cihhara K, Hashimoto Y: "Measurement of serum 20K human growth hormone by a novel ELISA"J Clin Endocrinol Metab. 84. 317-322 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Isozaki O, tsushima T, Miyakawa M, Nozoe Y, Demura H, Seki H.: "Growth hormone directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats"J Endcrinol. 161. 511-516 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa M, Tsuhima T, Murakami H, Isozaki O, Takano K: "Serum Jeptin levels and bloelectrical impedance assesment of body composition in patients with Graves disease and hypothyroidism"Endocrine J. 46. 665-673 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohomori N, Tsushima T, Sekine Y, Sato K, Shibagaki Y, Ijuji S, Takano K: "Gestational thyrotoxicosis with acute wernicke encephalopathy"Endocrine J. 46. 787-793 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamauchi T, Yamauchi N, Sugiyama T, Waki H, Miki H, Tone K, Tsuhima T., et al.: "Consitutive tyrosine phosphorylation of erbb-2 via jal2 by autocrine secretion of prolactin in human brast cancer"J Biol Chem. 275. 33937-33944 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T: "Severe thyrotoxicosis induced by thyroid metastasis ot lung denocarcinoma : a case report and rview of the literature"Thyroid. 11. 883-888 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsushima T, Kato Y, Miyachi Y, Teramoto A, Cihhara K, Hashimoto Y.: "Measurement of serum 20K human growth hormone by a novel ELISA"J Clin Endocrinol Metab. 84. 317-322 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Isozaki O, Tsushima T, Miyakawa M, Nozoe Y, Demura Seki H,: "Growth hormone directly inhibits leptin gene expression n visceral fat tissue in fatty Zucker rats."J Endcrinol. 161. 511-516 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa M, Tsushima T, Murakami H, Isozaki O, Takano K: "Serum leptin levels and bioelectrical impedance assesment of body composition in patients with Graves disease and hypothyroidism."Endocrine J. 46. 665-673 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Ohomori N, Tsushima T, Sekine Y, Sato K, Shibagaki Y, Ijuji S, Takano K: "Gearational thyrotoxicosis with acute Wemicke encephalopathy"Endocrine J. 46. 787-793 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamauchi T, Yamauchi N, Sugiyama T, Waki H, Miki Tone K, Matsuba S, Tsushima T et al: "Constitutive tyrosine phosphorylation of erbb-2 via jal2 by autocrine secretion of prolactin in human brast cancer"J Biol Chem. 275. 33937-33944 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Miyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T, Takano K: "Severe thyrofoxicosis induced by thyroid metastasis of lung denocarcinoma: a case report and rview of the literature"Thyroid. 11. 883-888 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Tsushima T, Kato Y, Miyachi Y, Teramoto A, Cihhara K, Hashimoto Y: "Measurement of serum 20K human growth hormone by a novel ELISA"J Clin Endocrinol Metab. 84. 317-322 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Isozaki O, Tsushima T, Miyakawa M, Nozoe Y, Demura H, Seki H: "Growth hormone directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats"J Endcrinol. 161. 511-516 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyakawa M, Tsushima T, Murakami H, Isozaki O, Takano K: "Serum leptin levels and bioelectrical impedance assesment of body composition in patients with Graves disease and hypothyroidism"Endocrine J. 46. 665-673 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ohomori N, Tsushima T, Sekine Y, Sato K, Shibagaki Y, Ijuji S, Takano K: "Gestational thyrotoxicosis with acute Wernicke encephalopathy"Endocrine J. 46. 787-793 (1999)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamauchi T, Yamauchi N, Sugiyama T, Waki H, Miki H, Tone K, Tsushima T et al.: "Constitutive tyrosine phosphorylation of erbB-2 via Jak2 by autocrine secretion of prolactin in human brast cancer"J Biol Chem. 275. 33937-33944 (2000)

    • Related Report
      2001 Annual Research Report
  • [Publications] Miyakawa M, Sato K, Hasegawa M, Nagai A, Sawada T, Tsushima T: "Severe thyrotoxicosis induced by thyroid metastasis of lung denocarcinoma : a case report and rview of the literature"Thyroid. 11. 883-888 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamauchi T, et al: "Constitutive tyrosine phosphorylation of erbb-2 via jal2 by autocrine secretion of prolactin in human breast cancer"Journal of Biological Chmeistry. 275. 33937-33944 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tsushima T, et al: "Serum concentrations of 20K human growth hormone in normal adults and patients with various endocrine disorders."Endocrine Jounal. 47(supple). 517-521 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Miyakawa M, et al: "Serum leptin levels and bioelectrical impedance assesment of body composition in patients with Graves disease and hypothyroidism."Endocrine Journal. 46(5). 665-673 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] MIYAKAWA M: "Serum leptin levels and bioelectrical impedance assessment of body composition in patients with Graves disease and hypothyrold"Endocrine Journal. 46(5). 665-673 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Isozaki O: "Growth hormone directly inhibits leptin gene expression in visceral fat tissue in fatty Zucker rats"Journal of Endocrinology. 161(3). 511-516 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Liu y J: "Effects of cytokines on production of IGFBPs from human fibroblasts in culture"Endocrine Journal. 46(supple). 563-566 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] TSUSHIMA T: "Measurement of Derum 20K human growth hormone by a novel ELISA"Journal of Clinical Endocrinology & Metabolism. 84(1). 317-322 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] MIYAKAWA M: "Effect of GH/IGF-1 axis on leptin production"Journal of clinical Endocrinology & Metabolism. 83(10). 3476-3479 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Yamauchi T: "GH and prolactin stimulates tyrosine pnosphorylation of insulin receptor substrate-1,-2 and-3, their association"Journal of Biological Chemistry. 72(25). 15719-15726 (1998)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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