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Epigenetic change associate with the development of urogenital tumors

Research Project

Project/Area Number 10470331
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Urology
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

OGAWA Osamu  Kyoto Univ.Graduate Sch.of Med., Prof, 医学研究科, 教授 (90260611)

Co-Investigator(Kenkyū-buntansha) KAMOTO Toshiyuki  Kyoto Univ.Graduate Sch.of Med., Lecturer, 医学研究科, 助手 (00281098)
TERAI Akito  Kyoto Univ.Graduate Sch.of Med., Asist.Prof, 医学研究科, 講師 (50243019)
KAKEHI Yoshiyuki  Kyoto Univ.Graduate Sch.of Med., Associ.Prof, 医学研究科, 助教授 (20214273)
NAKAMURA Eijirou  Kyoto Univ.Graduate Sch.of Med., Lecturer, 医学研究科, 助手 (90293878)
KINOSHITA Hldefumi  Kyoto Univ.Graduate Sch.of Med., Lecturer, 医学研究科, 助手 (30324635)
寺地 敏郎  京都大学, 大学院・医学研究科, 助教授 (50207487)
山田 仁  京都大学, 大学院・医学研究科, 助手
加藤 哲郎  秋田大学, 医学部, 教授 (40004642)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,900,000 (Direct Cost: ¥12,900,000)
Fiscal Year 2000: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 1999: ¥2,800,000 (Direct Cost: ¥2,800,000)
Fiscal Year 1998: ¥6,900,000 (Direct Cost: ¥6,900,000)
KeywordsUrological cancer / Bladder cancer / Prostate cancer / Methylation / Epigenetics / 尿路性器癌 / メテレーション / 遺伝子変異 / エピジェネティックス
Research Abstract

1) Chromosomes 8 and 9 have been considered to play important roles in the development of bladder cancer. By using the clinical samples of bladder cancer, we determined that an important loci exists on the short arm of chromosome 8, and at least 2 locus on chromosome 9 are associated with bladder carcinogenesis. In addition, we identified a candidate tumor suppressor gene on chromosome 9, named DBCCR1 gene, and analyzed the methylation-status of its promoter region in several bladder cancer cell lines. This experiment showed that the site or the degree of methylation in the DBCCR1 gene promoter showed diversity between the cell lines, and the methylation status was not correlated with the level of expression of DBRCC1. The methylation of DBRCC1 gene was identified in 36 of 69 human bladder tumors (52%).
2) Telomerase is an RNA-dependent DNA polymerase, which can add telomeric repeats to the end of the chromosome, and this enzyme has been considered to have an important role in the cellular immortality. This gene is expressed in some stem cells including germ cells and down-regulated in normal somatic cells. In human cancer, however, this gene is re-expressed presumably by a certain epigenetic mechanism. In this study, we proposed that telomerase activity is a useful marker for the prediction of malignant potential of adrenal tumors, and the detection of telomerase activity in urine is a sensitive non-invasive diagnostic tool.
3) To identify the genetic predisposition to the prostate cancer, a molecular epidemiological analysis was conducted using blood DNA samples obtained from Japanese patients with prostate cancer. We clarified that the genetic polymorphisms in vitamin D receptor gene, CYP17 gene and E-cadherin gene are associated with the risk of prostate cancer.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (24 results)

All Other

All Publications (24 results)

  • [Publications] Kinoshita H,Ogawa O: "Telomerase activity in adrenal cortical tumors and pheochromocytomas with reference to clinicopathologic features."Urol.Res.. 26. 29-32 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsumori K,Ogawa O.: "Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH): Correlation with adenoma growth."Prostate. 41. 253-257 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada Y.,Ogawa O.: "Measurement of polymorphic trinucleotide repeats in the androgen receptor gene by matrix-assisted mass spectromenry."J.Mass Spectrom.,. 34. 885-888 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Habuchi T,Ogawa O: "Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostate hyperplasia in Japanese population."Cancer Res.,. 60. 305-308 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Habuchi T,Ogawa O: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect."Cancer Res.,. 60. 5710-5713 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wu XX,Ogawa O.: "Telomerase activity in urine after transurethral resection of superficial bladder cancer and early recurrence."Int J Urol.. 7. 210-217 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kinoshita H, Ogawa O, Mitsumori K, Kakehi Y, Terachi T, Yoshida O.: "Low frequency of positive telomerase activity in a chromophobe cell type of renal cell carcinoma."J.Urol.. 159. 245-251 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kinoshita H, Ogawa O, Mishina M, Oka H, Okumura K, Yamabe H, Terachi T, Yoshida O.: "Telomerase activity in adrenal cortical tumors and pheochromocytomas with reference to clinicopathologic features."Urol.Res.. 26. 29-32 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsumori K, Terai A, Oka H, Segawa T, Ogura K, Yoshida O, Ogawa O.: "Androgen receptor CAG repeat length polymorphism in benign prostatic hyperplasia (BPH) : Correlation with adenoma growth."Prostate. 41. 253-257 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wada Y., Mitsumori K., Terachi T., Ogawa O.: "Measurement of polymorphic trinucleotide repeats in the androgen receptor gene by matrix-assisted laser desorption/ionization time-of-flight mass spectromenry."J.Mass Spectrom.. 34. 885-888 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Habuchi T, Suzuki T, Sasaki R, Wang L, Sato K, Satoh S, Akao T, Tsuchiya N, Shimoda N, Wada Y, Koizumi A, Chihara J, Ogawa O, Kato T.: "Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostate hyperplasia in Japanese population."Cancer Res.. 60. 305-308 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Habuchi T, Liqing Z, Suzuki T, Sasaki R, Tsuchiya N, Tachiki H, Shimoda N, Satoh S, Sato K, Kakehi Y, Kamoto T, Ogawa O and Kato T.: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism with a gene dosage effect."Cancer Res.. 60. 5710-5713 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Wu XX, Kakehi Y, Takahashi T, Habuchi T, Ogawa O.: "Telomerase activity in urine after transurethral resection of superficial bladder cancer and early recurrence."Int J Urol.. 7. 210-217 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Habuchi T and Ogawa O et.al: "Association of vitamin D receptor gene polymorphism with prostate cancer and benign prostate hyperplasia in Japanese population."Cancer Research. 60. 305-308 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Habuchi T and Ogawa O et.al: "Increased risk of prostate cancer and benign prostatic hyperplasia associated with a CYP17 gene polymorphism"Cancer Research. 60. 5710-5713 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Habuchi T and Ogawa O et.al: "Hypermethylation at 9q32-33 tumor suppressor region is age-related in normal urothelium"Oncogene. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kinoshita H.et al.: "Telomerace activity in adrenal contical tumors"Urol. Res.. 26. 29-32 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kinoshita H.et al.: "Low frequency of positive telomerace activity in RCC"J. Urol. 159. 245-251 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sato K.et al.: "Expression of VEGF and its recepter H(t-1) in BT"Tohoku J Exp med.. 185. 173-184 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohgaki K.et al.: "Localization of tumor suppressor gene associated with BT"Genes Chromosomes Cancer. 25. 1-5 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Mitsunori K.: "Androgenes receptor CAG repeat length polynurphisms"Prostate. 41. 253-257 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ohgaki K.et al: "Two tangert regions of allelic loss on dnomicine 9"Jpn J. Cancer. Res. 90. 957-964 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kinoshita H, Ogawa O: "Low frequency of positive telomerase activity in a diromophope cell type of renal cell conviens" J.Urol. 159. 245-251 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Kinoshita H, Ogawa O: "Tetramerase actavity in adrenocorticel tumors and pheiochnirocytes with referance to chrico pathologic features" Urol, Res.26. 29-32 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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