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Inactivation model of human Adenomatous Polyposis Coli gene by using budding yeast in vivo.

Research Project

Project/Area Number 10470129
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Gastroenterology
Research InstitutionTohoku University

Principal Investigator

KANAMARU Ryonosuke  Department of Clinical Oncology, Institute of Development Aging & Cancer (IDAC) Tohoku University Professor, 加齢医学研究所, 教授 (70152783)

Co-Investigator(Kenkyū-buntansha) SUZUKI Takao  Department of Medical Oncology, Tohoku University Medical Hospital, Instrutor, 医学部・附属病院, 助手 (90292276)
SHIBATA Hiroyuki  Department of Clinical Oncology, Institute of Development Aging & Cancer (IDAC), Tohoku University Instructor, 加齢医学研究所, 助手 (50260071)
ISHIOKA Chikashi  Department of Clinical Oncology, Institute of Development Aging & Cancer (IDAC), Tohoku University Assistant professor, 加齢医学研究所, 助教授 (60241577)
加藤 俊介  東北大学, 加齢医学研究所, 助手 (40312657)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥12,800,000 (Direct Cost: ¥12,800,000)
Fiscal Year 2000: ¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥7,400,000 (Direct Cost: ¥7,400,000)
KeywordsAPC / Yeast / SC assay / tumor suppressor gene / carcinogen / mismatch repair system / colorectal tumor / stop codon assay
Research Abstract

Human APC gene plays the most important role of colorectal tumorigenesis, so we investigate to reveal the inactivation mechanism by using budding yeast. We presumed 2 type of inactivation mechanism : one is DNA replication error will cause the mutation of APC and the next reason is chemical carcinogen will cause the mutation. We has a good method to detect the mutations of long size DNA fragment, what we call, yeast stop codon assay. Yeast stop codon assay is very useful to detect the protein truncating mutation such as frameshift mutation and nonsense mutation.
On the first step, we performed some yeast cell lines those defects yeast mlh1, msh2, pms1, pms2 genes. At the result, the most good model of yeast mutation assay is msh2 defect cell lines to detect the mutation of human APC gene in yeast cells. The next, we analyzed the mutation cluster region of human APC gene and we detected more highly frequent mutation rate of APC mutation than that of wild type yeast msh2 cell lines. Most … More mutations in msh2 defect yeast cells were insertion of deletion mutations are most frequent in APC simple reapeat sequence. On the other hand, most mutations in wild type yeast cells were nonsense mutation we detected until now. So the inactivation mechanism has the feature of mutation spectrum of APC gene so that we might presume the inactivation mechanism in the clinical materials of colorectal tumors.
The patients who has more than 6 polyps of colon has much risk of colorectal carcinogenesis in general. So we collected lots of chinical materials of colorectal polyps in our related hospitals. we extracted the nuculeic acid from all each tumors and analyzed the MCR region of APC gene. We easily detected APC mutation by using stop codon assay or modified stop codon assay. APC mutations of each polyps of one individual were not the same part of APC gene, so we cannot detect rare polymorphism to occur that would make the error of DNA replication. Now we cannot finish the APC mutation data base in the yeast models, so we need to attempt to analyze human APC gene of more number of yeast samples and human clinical materials. Less

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Suzuki T,Ishioka C,kato S,Mitachi Y, et al.: "Detection of APC mutations by a Yeast-based Protein Truncation Test(YPTT)."Genes Chromosome & Cancer. 21. 290-297 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Osada M,Ishioka C,Kanamaru R,Shun Taro I, et al.: "Cloning and funtional analysis of human p51,which structually and functionally resembles p53"Nature Medcine. 4-7. 839-843 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimodaira H,Shibata H,Suzuki T,Kanamaru R,Ishioka C et al.: "Functional analysis of human MLH1 mutations in Saccharomyces cerevisidae"Nature Genetics. 19. 384-389 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Simada A,Kanamaru R,Ishioka C, et al.: "The transcriptional Activities of p53 and Its Homologue p51/p63;Similarities and Differences"Cancer Reserch. 59. 2781-2786 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sunahara M,Ishioka C,Ikawa S et al.: "Mutational analysis of p51/p63,a p53 homologue,in non small cell lung cancer and breast cancer"Oncogene. 18. 3761-3765 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato S,Kanamaru R,Ishioka C et al.: "Effects of p51/p63 Missense mutations on Transcriptional Activities of p53 Downstream genes Prometers."Cancer Reserch. 59. 5908-5911 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Han SH,Suzuki T,Shibata H,Ishioka C,Kanamaru R, et al.: "Functional elaluation of pTEN missense mutations using in vitro phosinositide phosphatase assay."Cancer Reserch. 60. 3147-3151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kato H,Suzuki T,Shibata H,Ishioka C,Kanamaru R et al.: "Functional evaluation of p53 and pTEN Mutations in Gliomas."Clinical Cancer Reserch. 6. 3937-3943 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Chikashi Ishioka, Takao Suzuki, Masato Sakayori, Akira Shimada, Ryunosuke Kanamaru: "Screening of the mutations of tumor suppressor genes by stop codon assay."Rinsho Kagaku. 34 (3). 368-373 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ryunosuke Kanamaru, Takao Suzuki: "Genetic diagnosis of familial colorectal tumor by using budding yeast cells."Journal of the Japanese Society of Gastroenterology. 96. 131-136 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Takao Suzuki, Ryunosuke Kanamaru: "Genetic background of Carcinogenesis."Japanese Journal of Cancer Chemotherapy. 26 (13). 1971-1979 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Suzuki T,Ishioka C,Kato S., Mitachi Y, et al.: "Detection of APC mutations by a Yeast-based Protein truncation Test (YPTT)."Genes Chromosome & Cancer. 21. 290-297 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Osada M,Ishioka C,Kanamaru R,Shuntaro I. et al.: "Cloning and functional analysis of human p51,which structurally and functionally resembles p53"Nature Medcine. 4-7. 839-843 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimodaira H,Shibata H,Suzuki T,Kanamaru R,Ishioka C et al.: "Functional analysis of human MLH1 mutations in saccharomyces cevevisidae"Nature Genetics. 19. 384-389 (1998)

    • Related Report
      2000 Annual Research Report
  • [Publications] Simada A,Kanamaru R,Ishioka C et al.: "The transcriptional Activities of p53 and Its Homologue p51/p63 : Similarities and Differences"Cancer Research. 59. 2781-2786 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sunahara M,Ishioka C,Ikawa S et al.: "Mutational analysis of p51/p63, a p53 homologene, in non small cell lung cancer and breast cancer"Oncogene. 18. 3761-3765 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato S,Kanamaru R,Ishioka C et al.: "Effects of p51/p63 Missense mutations on Transcriptional Activities of p53 Downstream genes Promoters."Cancer Research. 59. 5908-5911 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Han SH,Suzuki T,Shibata H,Ishioka C,Kanamaru R, et al.: "Functional elaluation of _pTEN missense mutations using in vitro phosinositide phosphatase assay."Cancer Research. 60. 3147-3151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kato H,Suzuki T,Shibata H,Ishioka C,Kanamaru R et al.: "Functional evaluation of p53 and pTEN Mutations in Gliomas."Clinical Cancer Research. 6. 3937-3943 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] 下平 他: "Functional analysis of human MLI nutations in Saccharomyces cerevisiae"Nature genetics. 19. 384-389 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木 他: "Detection of APC nutations by a yeast-based Protein tyuncation test"Genes, Chromosome & Cancer. 21. 290-297 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] 金丸 他: "出芽酵母を用いた家族性大腸腫瘍の遺伝子診断法"日本消化器病学会雑誌. 96. 131-136 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 鈴木 他: "がんの遺伝的感受性-発がんの遺伝的要因とその診断法-"癌と化学療法. 26. 1971-1979 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 島田 他: "The transcriptional activities of P53 and its homologue P51/P63: similarities and defferences"Cancer Research. 59. 2781-2786 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 加藤 他: "Effects of P51/P63 misserse nutations on Transcriptional activities of P53 downstream gene promoters,"Cancer Research. 59. 5908-5911 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takao Suzuki et.al.: "Detection of APC mutations by a Yeast-Based Protein Truncation Test." Genes,Chromosome & Cancer. 21. 290-297 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shimodaira et al.: "Functional analysis of human MLH1 mutations in Saccharomyces crevisiae." Nature Genetics. 19. 384-389 (1998)

    • Related Report
      1998 Annual Research Report

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

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