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Novel Therapeutic Strategy Based on Systematic Regulation of Metastasis-related Genes Expression in Human Transitional Cell Carcinoma of the Urinary Bladder

Research Project

Project/Area Number 15591692
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKochi University

Principal Investigator

INOUE Keiji  Kochi Medical School, Associate Professor, 医学部, 助教授 (00294827)

Co-Investigator(Kenkyū-buntansha) KARASHIMA Takashi  Kochi Medical School, Research Associate, 医学部, 助手 (60304672)
SHUIN Taro  Kochi Medical School, Professor, 医学部, 教授 (80179019)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2004: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2003: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsDNA methylation / metastasis-related gene / transitional cell carcinoma / 移行上皮癌 / E-cadherin / 膀胱移行上皮癌 / 浸潤 / 転移
Research Abstract

Purpose : To assess the role of DNA methylation of metastasis-related genes (matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and E-cadherin) promoter region in transitional cell carcinoma (TCC).
Experimental Design : The following 9 human TCC cell lines were used :T24, EJ-1,HT-1197,RT4,253J-P,253J-BV, UM-UC-14,NS and KMBC-2. Normal renal proximal tubule cell line RPTEC and normal human umbilical vein endothelial cell line HUVEC was cultured in the recommended growth medium. 22 TCCs and matched adjacent normal tissues were obtained from 22 Japanese TCC patients by surgical resection at the Kochi Medical School. The DNA methylation of metastasis-related genes promoter region in these TCCs was identified by methylation specific PCR (MSP) method (E-cadherin) and combined bisulfite restriction analysis (COBRA) method (MMP2,MMP9,TIMP1,TIMP2). The induction of gene re-expression was also examined by treatment with 5-aza-deoxycytidine (5-aza) and trichostatin A (TSA).
Results : E-cadherin RNA expression was not detected by RT-PCR in T24 and EJ-1, and also TIMP2 in HT-1197 and KMBC-2. Each gene DNA methylation was detected in these cell lines. There was no difference of metastasis-related genes DNA methylation in other cell lines and surgical specimens. E-cadherin gene re-expression was induced by treatment with 5-aza-deoxycytidine (5-aza) and/or trichostatin A (TSA) in T24 and EJ-1, but TIMP2 gene was not in HT1197 and KMBC-2.
Conclusions : DNA methylation of the promoter region may be involved in the regulation of E-cadherin RNA expression. However, the role of DNA methylation of the promoter region in other metastasis-related genes (MMP and TIMP) could not be clarified in present study.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (7 results)

All 2005 2004 2003

All Journal Article (7 results)

  • [Journal Article] Effect of combination therapy with a novel bisphosphonate, minodronate (YM529), and docetaxel on a model of bone metastasis by human transitional cell carcinoma2005

    • Author(s)
      Inoue K
    • Journal Title

      Clin Cancer Res 11

      Pages: 6669-6677

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of combination therapy with a novel bisphosphonate, minodronate (YM529), and docetaxel on a model of bone metastasis by human transitional cell carcinoma.2005

    • Author(s)
      Inoue K, Karashima T, Fukata S, Nomura A, Kawada C, Kurabayashi A, Furihata M, Ohtsuki Y, Shuin T
    • Journal Title

      Clin Cancer Res (Sep 15) 11(18)

      Pages: 6669-6677

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 腫瘍内新生血管を標的とした分子標的治療2004

    • Author(s)
      井上啓史
    • Journal Title

      西日本泌尿器科 66

      Pages: 425-432

    • NAID

      10017396924

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular target therapy for advanced bladder cancer2003

    • Author(s)
      Inoue K
    • Journal Title

      Nippon Rinsho 61

      Pages: 551-557

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Docetaxel (Taxotare) Enhances the Therapeutic Effect of the Angiogenesis Inhibitor TNP-470 (AGM-1470) in Metastatic Human Transitional Cell Carcinoma2003

    • Author(s)
      Inoue K
    • Journal Title

      Clin Cancer Res 12

      Pages: 886-899

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Molecular target therapy for advanced bladder cancer.2003

    • Author(s)
      Inoue K
    • Journal Title

      Nippon Rinsho vol.61, suppl.8

      Pages: 551-557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Docetaxel (Taxotare) Enhances the Therapeutic Effect of the Angiogenesis Inhibitor TNP-470 (AGM-1470) in Metastatic Human Transitional Cell Carcinoma2003

    • Author(s)
      Inoue K, Chikazawa M, Fukata S, Yoshikawa C, Shuin T.
    • Journal Title

      Clin Cancer Res (Feb) 9(2)

      Pages: 886-899

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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