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Early diagnosis of malignant pheochromocyToma by melecular biological method.

Research Project

Project/Area Number 09671075
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内分泌・代謝学
Research InstitutionTokyo Women's Medical University

Principal Investigator

NARUSE Mitsuhide  Tokyo Women's Medical University, Fuclty of Medicine, Associate Professor, 医学部, 助教授 (40120018)

Co-Investigator(Kenkyū-buntansha) NISHIKAWA Toshirou  Tokyo Women's Medical University, Fuclty of Medicine, Associate Professor, 医学部, 助教授 (50120019)
Project Period (FY) 1997 – 1998
Project Status Completed (Fiscal Year 1998)
Budget Amount *help
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1998: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 1997: ¥1,900,000 (Direct Cost: ¥1,900,000)
Keywordspheochromocytoma / malignant pheochromocytoma / early diagnosis / suppressor gene / p53 protein / adrenocortical tumor / 免疫組織化学染色
Research Abstract

To explore the clinical significance of p53 in the pathogenesis of adrenal neoplasms, we investigated the incidence of p53 gene mutations in functioning human adrenal tumors using the polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) technique to screen p53 exons 4 to 9. We examined 29 adrenocortical adenomas (primary aldosteronism, n=17 ; Cushing's syndrome, n=12, all benign), and 33 pheochromocytoma (benign solitary, n=18 ; benign multiple, n=5 ; malignant, n=1O) in Japanese and Chinese patients. PCR-SSCP did not show any abnormal band-shifts in any of the adrenocortical adenoma and benign solitary pheochromocytoma tissues. In contrast, six pheochromocytoma tissues (two cases benign multiple, four cases malignant) showed PCR-SSCP band-shifts. Subsequent DNA sequencing analysis of the shifted bands demonstrated that three cases contained point mutations within intronic regions, one case a silent mutation in exon 8, and three cases contained missense mutations (one case each in exons 5, 6 and 9). Immunohistochemical staining demonstrated that two of three cases with missense mutations and one case with an intronic mutation over-expressed p53 protein in tumor cell nuclei. As p21/WAF-l/CIP-1, a downstream mediator of p53, was expressed only in scattered pheocromocytoma tumor cell nuclei, we observed no association between p21/WAF-1/CIP-1 expression and mutation or over-expression of p53. The relatively high incidence of p53 gene mutations in multiple and malignant pheochromocytoma, but not in benign solitary cases, suggests that p53 mutation could play an important role in the pathogenesis of multiple and/or malignant pheochromocytoma. However, p53 mutations do not appear to play a role in the tumorgenesis of functioning adrenocortical adenoma.

Report

(3 results)
  • 1998 Annual Research Report   Final Research Report Summary
  • 1997 Annual Research Report
  • Research Products

    (22 results)

All Other

All Publications (22 results)

  • [Publications] Yoshimoto T.: "The relatively high frequency of p53 gene mutation in multiple and malignant pheochromocytoma in Japanese and Chinese patients." J.Endocrinol.159. 247-255 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto T.: "Potentiation of nathuretic peptide action by β-adrenergic blocker carvedilol in hypertensive rats : a new antihyper Tensive mechanism" Endocrinology. 139. 81-88 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanabe A.: "ET-1 and eNOS gene expression in the cardiovascular tissues of SHRSP/Izm effect of angiotensin convertig enzyme inhibitor aracepril." J.Cardiovasc. Pharmacol.31. S395-S398 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naruse M.: "Differential rolen of angiotensin receptor subtypes in adrenocortical function in mice." Life Sci.63. 1593-1598 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanabe A.: "Angiotensin II stimulates both aldosterone secretion and DNAsynthesis via type 1 but not type 2 receptors in bovine adrenocortical cells." J.Endocrinol. Invest.21(in press). (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogata M.: "Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy." J.Cardiovasc. Pharmacol.31. S378-S379 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto T.et al.: "The relatively high frequency of p53 gene mutation in multiple and malignant pheochromocytoma." J.Endocrinol.159. 247-255 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto T.et al.: "Potentiation of natriuretic peptide action by beta-adrenergic blocker carvedilol in hypertensive rats : a new antihypertensive mechanism." Endocrinology. 139. 81-88 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanabe A.et al.: "ET-1 and eNOS gene expression in the cardiovascular tissues of SHR-SP/Izm : effect of angiotensin converting enzyme inhibitor aracepril." J.Cardiovasc. Pharmacol.31(suppl.1). s395-s398 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Naruse M.et al.: "Deferential roles of angiotensin receptor subtypes in adrenocortical function in mice." Life Sci.63(18). 1593-1598 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Tanabe A.et al.: "Angiotension II stimulates both aldosterone secretion and DNA synthaesis via type 1 but not type 2 receptors in bovine adrenocortical cells" J.Endocrinol. Invest.21(in press). (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Ogata M.et al.: "Immunoreactive endothelin levels in the vitreous fluid are decreased in diabetic patients with proliferative retinopathy." J.Cardiovasc. Pharmacol.31(suppl.1). s378-s379 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1998 Final Research Report Summary
  • [Publications] Yoshimoto T.: "The relatively high frequency of p53 gene mutation in multiple and malignant pheochromocytoma in Japanese and Chinese patients" J.Endocrinol.159. 247-255 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Yoshimoto T.: "Poteutiation of natriuretic peptide action by β-adrenergic blocker carvedilol in hypertensive rats: a new autihypertensive mechanism" Endocrinology. 139. 81-88 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanabe A.: "ET-1 and eNOS gene expression in the cardiovascular tissuer of SHRSP/Izm : effect of angiotensin converting enzyme inhibitor aracepril." J.Cardiovasc. Pharmacol.31. S395-S398 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naruse M.: "Differential rolen of angiotensin receptor subtypes in adrenocortical function in mice." Life Sci.63. 1593-1598 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanabe A.: "Angiotensin II stimulates both aldosterone secretion and DNA synthesis via type 1 but not type 2 receptors in bovine adrenucortical cells." J.Endocrinol. Invest.21(in press). (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Ogata M.: "Immunoreactive endothelin levels in the Vitreous fluid are decrecised in diabetic patients with proliferative retinopathy." J. Cardiovasc. Pharmacol.31. S378-S379 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Naruse M.: "Renin/angiotensin/aldosterone system in maligrant hypertension." Internal Medicine. 36. 669-671 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanabe A.: "Left ventricular hypertrophy is more prominaut in patieuts with primary aldosleronism than in patieuts with other type of secondary hypertension" Hypertension Res.20. 85-90 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Zerg ZP: "Immunoreactive evdothelin-1 and its receptors in human adrenal tissues." J.Cardiovascular. Pharmacol.31(S1). S212-S214 (1998)

    • Related Report
      1997 Annual Research Report
  • [Publications] Tanabe A.: "Gene expression and roles of angiotensin II type 1 and type 2 receptors in human adrenals." Hormone Metab Res.(in press). (1998)

    • Related Report
      1997 Annual Research Report

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Published: 1997-04-01   Modified: 2016-04-21  

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