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Prediction of prognosis and clinical application of gene methylation score in urothelial cancers

Research Project

Project/Area Number 18591761
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

NAKAGAWA Masayuki  Kagoshima University, Graduate School of Medical and Dental Sciences, Professor (90164144)

Co-Investigator(Kenkyū-buntansha) ENOKIDA Hideki  Kagoshima University, Graduate School of Medical and Dental Sciences, Senior Assistant Professor (80347103)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,920,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥420,000)
Fiscal Year 2007: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2006: ¥2,100,000 (Direct Cost: ¥2,100,000)
Keywordsgene methylation / urothelial cancer / bladder cancer / tumor suppressor gene / methylation score / prediction of prognosis / collagen type 1 A2 / p16INK4a / p14ARF / DNA microarray法 / 細胞周期関連遺伝子
Research Abstract

Purpose : Many genes responsible for the bladder cancer progression have been isolated recently. We have reported that
hypermethylation of 2 tumor suppressor genes, pl6INK4a and p14ARF is involved in poor prognosis and tumor invasiveness in patients with bladder cancer. In the present study, we examined methylation status of collagen 1A2 gene promoter region in terms of prediction of patient prognosis.
Materials and Methods : We examined methylation status of collagen 1A2 gene in the presence and absence of demethylation agent, 5 aza-cytizine in human BOY cultured bladder cancer cells. We examined the frequency of methylation of collagen 1A2 gene in 97 clinical specimens from radical cystectomy and TURBT. Furthermore, we transfected collagen 1A2 gene into human bladder cancer cells and examined cell migration ability and growth rate in both transfectants and control cells.
Results : Gene expression of collagen 1A2 gene was increased by 5 aza-cytizine treatment. Collagen 1A2 gene expression in bladder tumors was significantly lower than that in normal bladder tissues. Methylation scores in the bladder tumors are significantly higher that those in normal bladder tissues. Cell migration and growth rate in collagen 1A2 gene transfectants are significantly decreased compared to those in control cells.
Conclusions : Collagen 1A2 gene expression is suppressed by the promoter methylation in human bladder cancers. These results suggest that collagen 1A2 gene plays a role in tumor suppressor in human bladder cancer.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (19 results)

All 2007 2006

All Journal Article (12 results) (of which Peer Reviewed: 5 results) Presentation (7 results)

  • [Journal Article] Epigenetic modifications of R.ASSF1A gene through chromatin remodeling in prostate cancer2007

    • Author(s)
      Kawamoto K, et. al.
    • Journal Title

      Clinical Cancer Research 13

      Pages: 2541-2548

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Increased SKP2 and CKSl gene expression contributes to the progression of human urothelial carcinoma2007

    • Author(s)
      Kawakami K, et. al.
    • Journal Title

      Journal of Urology 178

      Pages: 301-307

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Epigenetic modifications of RASSF1A gene through chromatin remodeling in prostate cancer2007

    • Author(s)
      Kawamoto, K, et. al.
    • Journal Title

      Clinical Cancer Res. 13

      Pages: 2541-2548

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Increased SKP2 and CKS1 gene expression contributes to the progression of human urothelial carcinoma2007

    • Author(s)
      Kawakami, K, et. al.
    • Journal Title

      J. Urol. 178

      Pages: 301-307

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Epigenetic modifications of RASSF1A gene through chromatin remodeling in prostate cancer.2007

    • Author(s)
      Kawamoto K, et. al.
    • Journal Title

      Clinical Cancer Research 13

      Pages: 2541-2548

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased SKP2 and CKS1 gene expression contributes to the progression of human urothelial carcinoma.2007

    • Author(s)
      Kawakami K, et. al.
    • Journal Title

      Journal of Urology 178

      Pages: 301-307

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] P161NK4a and p14ARF methylation as a potential biomarker for human bladder cancer2006

    • Author(s)
      Kawamoto, K., et. al.
    • Journal Title

      Biochemical and Biophysical Research Communications 339

      Pages: 790-796

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] P16INK4a and p14ARF methylation as a potential biomarker for bladder cancer2006

    • Author(s)
      Kawamoto, K, et. al.
    • Journal Title

      Biochem.Biophys Res Commun 339

      Pages: 790-796

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] p16INK4a and p14ARF methylation as a potential biomarker for human bladder cancer.2006

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

      Biochemical and Biophysical Research Communication 339・3

      Pages: 790-796

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Identification of differentially expressed genes in human bladder cancer through genome-wide gene expression profiling.2006

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

      Oncology Report 16・3

      Pages: 521-531

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Smoking influences aberrant CpG hypermethylation of multiple genesin human prostate carcinoma.2006

    • Author(s)
      Enokida H. et al.
    • Journal Title

      Cancer 106・1

      Pages: 79-86

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Combination analysis of hypermethylated Wnt-antagonist family gene as a novel epigenetic biomarker panel for bladder cancer detection.2006

    • Author(s)
      Urakami S. et al.
    • Journal Title

      Clinical Cancer Research 12・7pt1

      Pages: 2109-2116

    • Related Report
      2006 Annual Research Report
  • [Presentation] 膀胱癌進展における遺伝子メチル化の役割2007

    • Author(s)
      榎田 英樹, ほか
    • Organizer
      第95回日本泌尿器科学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
  • [Presentation] 膀胱癌におけるCOLIA2遺伝子プロモーター領域のメチル化の検討2007

    • Author(s)
      森 勝久, ほか
    • Organizer
      第95回日本泌尿器科学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 尿路上皮癌におけるSKP2とCI(S1の発現および臨床病理学的事項との関連2007

    • Author(s)
      川上 一盛, ほか
    • Organizer
      第95回日本泌尿器科学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of gene methylation in progression of bladder cancer2007

    • Author(s)
      Enokida, H, et. al.
    • Organizer
      95th Annual Meeting of Japanese Urological Association
    • Place of Presentation
      Kobe
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Roles of collagen 1A2 gene methylation in bladder cancer2007

    • Author(s)
      Mori, K, et. al.
    • Organizer
      95th Annual Meeting of Japanese Urological Association
    • Place of Presentation
      Kobe
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] Association between expression of SKP2 / CKS1 and clinicopathological parameters in human urothelial cancers2007

    • Author(s)
      Kawakami, K, et. al.
    • Organizer
      95th Annual Meeting of Japanese Urological Association
    • Place of Presentation
      Kobe
    • Year and Date
      2007-04-14
    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Presentation] 膀胱癌におけるCOL1A2遺伝子プロモーター領域のメチル化の検討2007

    • Author(s)
      森 勝久・他
    • Organizer
      第95回日本泌尿器科学会総会
    • Place of Presentation
      神戸市
    • Year and Date
      2007-04-14
    • Related Report
      2007 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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