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Roles of p51/p63 in the organogenesis, differentiation and carcinogenesis of the urothelium

Research Project

Project/Area Number 14571489
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionTokyo Medical and Dental University

Principal Investigator

KAWAKAMI Satoru  Tokyo Medical and Dental University, Department of Urology, assistant, 大学院・医歯学総合研究科, 助手 (80313261)

Co-Investigator(Kenkyū-buntansha) FUJII Yasuhisa  Tokyo Medical and Dental University, Department of Urology, 医学部附属病院, 助手 (70282754)
KAGEYAMA Yukio  Tokyo Medical and Dental University, Department of Urology, Associate Professor, 大学院・医歯学総合研究科, 助教授 (10211153)
KIHARA Kazunori  Tokyo Medical and Dental University, Department of Urology, Professor, 大学院・医歯学総合研究科, 教授 (40161541)
Project Period (FY) 2002 – 2003
Project Status Completed (Fiscal Year 2003)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2003: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2002: ¥2,200,000 (Direct Cost: ¥2,200,000)
Keywordsp51 / p63 / p53 / urothelium / cytodifferentiation / transitional cell carcinoma / basal cell / β-catenin / prognostic factor / uroplakin
Research Abstract

Expression profile of p63 in the human urothelial cells
Expression profiles of p63 protein and mRNA in the primary culture of human urothelial cells and human urothelial carcinoma cell lines in vitro were examined using immunocytochemistry and RT-PCR Human urothelial basal cells strongly express ΔNp63 isoform. This ΔNp63 expression was preserved in well differentiated human urothelial carcinoma cell lines, while was impaired in poorly differentiated human urothelial carcinoma cell lines.
Expression profile of p63 in normal human urothelial tract and urothelial carcinoma tissue
Expression profiles of p63 protein and p63 mRNA isoforms were examined in the normal human urinary tract and human bladder cancer tissues using immunohistochemishy and RT-PCR assay, respectively. In the normal human urinary tract, p63 was expressed in the nucleus of urothelial cells in the basal to intermediate layer and only ΔN isoform was expressed. This expression pattern was preserved in well differentiated, non … More -invasive bladder cancers, while was diminished or disappeared in poorly differentiated, invasive bladder cancers. This in vivo finding was in good agreement with the aforementioned in vitro finding.
In the invasive bladder cancer tissue, we found a significant association of decreased ΔNp63 expression with decreased β-catenin expression that has been known to associate with progression of the disease. Since possible role of p63 in the regulation of β-catenin gene expression has been recently suggested, our results indicated that down-regulation of ΔNp63 expression may be one of the causes of β-catenin down regulation.
Prognostic significance of ΔNp63 expression in invasive bladder cancer
ΔNp63 expression was examined in surgically removed invasive bladder cancer tissue. Prognosis of patients with invasive bladder cancer treated with radical cystectomy was analyzed using multivariate analyses. We found that decreased ΔNp63 expression was significant and independent prognostic factors along with pT stage as well as pN stage in these patients. Less

Report

(3 results)
  • 2003 Annual Research Report   Final Research Report Summary
  • 2002 Annual Research Report
  • Research Products

    (10 results)

All 2003 2002 Other

All Journal Article (6 results) Publications (4 results)

  • [Journal Article] Impaired ΔNp63 expression characterises aggressive phenotypes of urolthelial neoplasns2003

    • Author(s)
      Koga F, Kawakami S, et al.
    • Journal Title

      British Journal of Cancer 88

      Pages: 740-747

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder2003

    • Author(s)
      Koga F, Kawakami S, et al.
    • Journal Title

      Clinical Cancer Research 15

      Pages: 5501-5507

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Impaired ΔNp63 expression characterizes aggressive phenotype of urothelial neoplasms.2003

    • Author(s)
      Koga F, Kawakami S, et al.
    • Journal Title

      British Journal of Cancer 88

      Pages: 740-747

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Impaired p63 expression associates with poor prognosis and uroplakin III expression in invasive urothelial carcinoma of the bladder.2003

    • Author(s)
      Koga F, Kawakami S, et al.
    • Journal Title

      Clinical Cancer Research 15

      Pages: 5501-5507

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Peroxisome proliferator-activated receptor γ ligands suppress proliferation of human urothelial basal cells in vitro2002

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

      Journal of Cellular Physiology 191

      Pages: 310-319

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Journal Article] Peroxisome proliferators-activated receptor γ ligands suppress proliferation of human urothelial basal cells in vitro.2002

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

      Journal of Cellular Physiology 191

      Pages: 310-319

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2003 Final Research Report Summary
  • [Publications] Koga F, Kawakami S, et al.: "Impaired ΔNp63 expression characterises aggressive phenotypes of urothelial neoplasms"British Journal of Cancer. 88. 740-747 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Fujii Y, Kawakami S, et al.: "Long-term outcome of bladder papillary urothelial neoplasms of low mailgnant potential"BJU International. 92. 559-562 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kawakami S, et al.: "Peroxisome proliferator-activated receptor γ ligands suppress proliferation of human urothelial basal cells in vitro"Journal of Cellular Physiology. 191. 310-319 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Koga F, Kawakami S, et al.: "Impaired ΔNp63 expression characterises aggressive phenotypes of urolthelial neoplasms"British Journal of Cancer. (in press). (2003)

    • Related Report
      2002 Annual Research Report

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Published: 2002-04-01   Modified: 2016-04-21  

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