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Association between malignant progression of colorectal adenomas and DNA replication error and inhibition of apoptosis

Research Project

Project/Area Number 07671437
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKinki University

Principal Investigator

WATATANI Masahiro  Kinki University School of Medicine, First Department of Surgery, Assistant professor, 医学部, 講師 (00220856)

Co-Investigator(Kenkyū-buntansha) HIDA Jin-ichi  Kinki University School of Medicine, Staff, 医学部, 助手 (20238306)
KUBO Ryuichi  Kinki University School of Medicine, Assistant professor, 医学部, 講師 (70225192)
Project Period (FY) 1995 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1996: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1995: ¥800,000 (Direct Cost: ¥800,000)
KeywordsDNA replication error / apoptosis / p53 / bcl-2 / colorectal carcinogenesis / Bcl-2遺伝子 / p21^<WAF1>遺伝子 / PCNA / p53 / bcl-2 / p21^<WAF-1> / 発癌ポテンシー / Microsatellite instability / p53染色 / bcl-2染色
Research Abstract

The aim of this study is to investigate the association between malignant potency of colorectal adenomas to progress to carcinoma and the inhibition of apoptosis and DNA replication errors in colorectal adenomas. We examined p53 and bcl-2 overexpression, and analyzed dinucleotide instability in colorectal adenomas showing various degree of dysplasia and carcinomas invading submucosa. Overexpression of p53 was associated with progression dysplasia and depth of cancer invasion. However, the frequency of bcl-2 overexpression was not increased according to the degree of dysplasia. We also studied p21 WAF1 and PCNA expression in adenomas with various degree of dysplasia and carcinomas with submucosal invasion, and investigated whether the irregularity of cell cycle was related to the development of colorectal tumors. In adenomas showing high grade dysplasia, the PCNA labeling index in adenomas which were positive for p21 WAF1 and negative for p53 overexpression was significantly lower than in adenomas which were both positive for p21 WAF1 and p53 overexpression. These results suggest that proliferation of some of adenomas with high grade dysplasia might be suppressed by p21 WAF1 expression which was induced irrespective of p53 expression. The analysis of genetic alterations in carcinomas showed that 27% of 87 tumors had DNA replication error. We undertook analysis of DNA replication error in DNAs from formalin-fixed paraffin-embedded adenomas, but efficiency of PCR amplification of such DNAs was not so good to perform the study. Further study is necessary to clarify the role of DNA replication error in colorectal carcinogenesis.

Report

(4 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • 1995 Annual Research Report
  • Research Products

    (29 results)

All Other

All Publications (29 results)

  • [Publications] M.Watatani, et al: "Allelic loss of chromosome 17p,mutation of the p53 gene,and microsatellite instability in right-and left-sided colorectal cancer" Cancer. 77. 1688-1693 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watatani, et al: "Bcl-2 and p53 expression in metachronous colorectal adenomas compared with initial adenomas in relation to the degree of dysplasia" Recent,advanced in Gastronterological carcinogenesis. 371-375 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kuroda, M.Watatani, et al: "Expression of p53,p21WAF1 and bcl-2 during colorectal tumorigenesis" Recent advanced in Gastroenterological Carcinogenesis. 365-369 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Ieda, M.Watatani, et al.: "Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas" Surg Today. 26(4). 230-235 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Yoshida, M.Watatani: "Relationship of changes of p53 gene and microsatellite instability toprogression of colorectal cancer." Acta Med kinki Univ. 20(4). 369-376 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 家田 眞太郎, 綿谷 正弘: "大腸癌切除後異時性腺腫発生におけるp53遺伝子蛋白発現とbcl-2遺伝子蛋白発現の生物学的役割-初発腺腫との比較から-" 日本大腸肛門病会誌. 49(3). 191-198 (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watatani, et al: "Bcl-2 and p53 expression in metachronous colorectal adenomas compared with initial adenomas in relation to the degree of dysplasia" Recent advanced in Gastronterological carcinogenesis. 371-375 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] K.Kuroda, M.Watatani, et al: "Expression of p53, p21 WAF1 and bcl-2 during colorectal carcinogenesis" Recent advanced in Gastronterological carcinogenesis. 365-369 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watatani, et al: "Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right-and left-sided colorectal cancer" Cancer. 77. 1688-1693 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] S.Ieda, M.Watatani, et al.: "Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas" Surgery Today. 26. 230-235 (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] T.Yoshida, M.Watatani: "Relationship of changes of p53 gene and microsatellite instability to progression of colorectal cancer" Acta Med Kinki Univ. 20. 365-376 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Inui, M.Watatani, et al.: "Genetic alterations in sporadic colorEctal carcinomas at all clinical stagesof progression" Acta Med Kinki Univ. 20. 13-22 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] M.Watatani, et al: "Allelic loss of chromosome 17p,mutation of the p53 gene,and microsatellite instability in right-and left-sided colorectal cancer" Cancer. 77. 1688-1693 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Watatani, et al: "Bcl-2 and p53 expression in metachronous colorectal adenomas compared with initial adenomas in relation to the degree of dysplasia" Recent advanced in Gastronterological carcinogenesis. 371-375 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] K.Kuroda, M.Watatani, et al: "Expression of p53,p21 WAF1 and bcl-2 during colorectal tomorigenesis" Recent advanced in Gastronterological carcinogenesis. 365-369 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] S.Ieda, M.Watatani, et al.: "Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas and early carcinomas" Surg Today. 26(4). 230-235 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] T.Yoshida, M.Watatani: "Relationship of changes of p53 gene and microsatellite instability to progression of colorectal cancer." Acta Med kinki Univ. 20(4). 369-376 (1995)

    • Related Report
      1997 Annual Research Report
  • [Publications] 家田眞太郎, 綿谷正弘: "大腸癌切除後異時性腺腫発生におけるp53遺伝子蛋白発現とbcl-2遺伝子蛋白発現の生物学的役割-初発腺腫との比較から-" 日本大腸肛門病会誌. 49(3). 191-198 (1996)

    • Related Report
      1997 Annual Research Report
  • [Publications] 黒田幸作,綿谷正弘: "大腸癌進展における遺伝子変化" 癌と化学療法. 23. 164-168 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 家田真太郎,綿谷正弘: "大腸癌切除後異時性腺腫発生におけるp53遺伝子蛋白発現とbcl-2遺伝子蛋白発現" 日本大腸肛門病学会雑誌. 49巻・3号. 191-198 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masahiro Watatani.et al.: "Allelic loss of chromosome 17p,mutation of the p53 gene and microsatellite intability in right-and left sided colorectal cancer" Cancer. 77・8. 1688-1693 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] K.Kuroda.M.Watatani.et al.: "Expression of p53,p21^<WAF1>and bcl-2 during colorectal tumorigenesis" Recent Advances in Gastroenterological corcinogenesis. 365-369 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M. Watatani,et al.: "Bcl-2 and p53 expression in netachronous colorectal adenumas compared adenumas in relation to the deqrec of lyoplasia" Recent Advances in Gastroenterological Carcinogenesis. 371-375 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Masahiro Watatani: "Allelic loss of chromosome 17p, mutation of the p53 gene, and microsatellite instability in right-and left-sided colorectal cancer" Cancer. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] S. Ieda: "Immunohistochemical analysis of p53 and ras p21 expression in colorectal adenomas with varying degrees of dyoplasia and early carcinomas with and without adenomatous component" Surgery Today. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] Toshihiro Yoshida: "Relationship of changes of p53 gene and microsatellite instability to progression of colorectal cancer" Acta. Medica Kinki. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] 家田真太郎: "P53遺伝子蛋白発現とbcl-2遺伝子蛋白発現の生物学的役割-初発腺腫との比較から-" 日本大腸肛門病学会雑誌. (印刷中).

    • Related Report
      1995 Annual Research Report
  • [Publications] 家田真太郎: "大腸癌術後に発生する異時性腺腫は発癌性が強いが" 消化器癌の発生と進展. 6. 89-92 (1994)

    • Related Report
      1995 Annual Research Report
  • [Publications] 吉田年宏: "p53遺伝子異常と遺伝子不安定性から検討した右側・左側大腸癌の発癌機構" 消化器癌の発生と進展. 7. 411-413 (1995)

    • Related Report
      1995 Annual Research Report

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Published: 1995-04-01   Modified: 2016-04-21  

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