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ヒト胎盤形成及び癌化とゲノムインプリンティング

Research Project

Project/Area Number 08671904
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Obstetrics and gynecology
Research InstitutionKYUSHU UNIVERSITY

Principal Investigator

ARIMA Takahiro  Medical Institute of Bioregulation Kyushu Univ.Lecturer, 生体防御医学研究所, 助手 (80253532)

Co-Investigator(Kenkyū-buntansha) WAKE Norio  Medical Institute of Bioregulation Kyushu Unv.Professor, 生体防御医学研究所, 教授 (50158606)
KATO Hidenori  Medical Institute of Bioregulation Kyushu Univ.Assistant Professor, 生体防御医学研究所, 講師 (60214392)
NISHIDA Jun-ichi  Medical Institute of Bioregulation Kyushu Univ.Lecturer, 生体防御医学研究所, 助手 (40264113)
KATO Kiyoko  Medical Institute of Bioregulation Kyushu Univ.Lecturer, 生体防御医学研究所, 助手 (10253527)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsGennomic Imprinting / RLGS-M method / IGF2-H19 / Tumor Suppressor gene / Complete mole / normal villi / choriocarcinoma / ゲノムインプリティング / 胞状寄胎
Research Abstract

1. Systemic search for imprint genes.
We successful identified some imprint genes using RLGS-M method. As the examination sample we used androgenetic mole and normal placental villi. To data, we could get 12 candidate imprinted clones from about 4600 clones. We analyzed the DNA sequences of all 12 clones. The results were as follows, 3 clones were imprinted genes (GNAS1, SNRPN,hCGbeta), 6 clones were reported gene but not until identify the imprint one and 3 clones were unknown genes.
2. Association of IGF2 and H19 imprinting with choriocarcinoma development.
We have studied IGF2 and H19 expression, and methylation status of H19 gene in both the native and cultured choriocarcinomas. The CpG sites analyzed for methylation in the two allele-specific methylation regions, extended to the -2.0kb and -0.8kb upstream locus to the start of transcript. The majority of choriocarcinomas were characterized by high expression of H19. However, enhanced H19 expression was accompanied by hypermethylation … More of CpG sites over these regions. Sequence analysis of H19 promoter revealed a large number of mutations in this tumor. And "hot spot" of these mutations was located from the transcription initiation site to -300bp upstream of it, in which contained several transcriptional elements such as Sp1 binding site and CAAT box, and had significant homology to the mouse H19 corresponding region. These findings may suggest that choriocarcinomas carry important mutations to get over transcriptional suppression by CpG methylation.
Human chromosome 7 carries a putative tumor suppressor gene (s) involved in choriocarcinoma.
Tumorigenic revertants isolated from microcelI-hybrids with the introduced chromosome 7 contains reduced numbers of chromosome 7. These findings suggest that chromosome 7 contains a putative tumor suppressor gene (s) for choriocarcinoma. AIterations in tumorigenic phenotypes seen in microcell-hybrids were not associated with the presence of either ERV3 or H-plk locus located on the introduced chromosome 7, indicating the putative tumor suppressor gene (s) is outside of ERV3 and H-plk gene loci. Furthermore, we obtained evidence to define a critical region on chromosome 7 (7p12-7q11.23) that was frequently lost in surgically removed choriocarcinoma tissues and cell lines. Using a panel of microsatellite markers, biallelic deletions were observed, which strongly suggests the presence of a tumor suppressor gene (s) within this critical region. Less

Report

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

    (27 results)

All Other

All Publications (27 results)

  • [Publications] Arima T, et al: "Malignant trophoblestic Neoplasms with Different Modes of Origin." Cancer Genet Cytogenet. 85. 5-15 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arima T, et al: "Association of IGF2 and H19 imprinting with choriocarcinoma development." Cancer Genet Cytogenet. 93. 39-47 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mastuda T, et al: "Human chromosome 7carries a putative tumor suppressor gene(s)involved in choriocarcinoma." Oncogene. 15. 2773-2781 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N, et al: "Genetics of gestational trophoblastic diseases." CME Journal of Gynecol0gic Oncology. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N, et al: "Involvement of IGF2 and H19 imprinting in choriocarcinoma development." FIGO,Journal. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N, et al: "Genetics of gynecological cancer-molecular events implicated in trophoblastic neoplasia development." The proceeding of X V FIGO. in press.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 加藤 秀則 他: "癌の臨床" 発癌機序について, 1139-1148 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 有馬 隆博 他: "図説産婦人科VIEW" 絨毛生疾患におけるゲノムインプリンティング, 166-173 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arima T,et al: "Madignant trophoblastic Neoplasms with Different Modes of Origin." Cancer Genet Cytogenet. 85. 5-15 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arima T,et al: "Association of IGF2 and H19 imprinting with choricarcinoma development." Cancer Genet Cytogenet. 93. 39-47 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Mastuda T,et al: "Human chromosome 7 carries a putative tumor suppressor gene (s) involved in choriocarcinoma." Oncogene. 15. 2773-2781 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N,et al: "Genetics of gestational trophoblastic diseases." CME Journal of Gynecologic Oncology. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N,et al: "Involvement of IGF2 and H19 imprinting in choriocarcinoma development." FIGO,Journal. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Wake N,et al: "Genetics of gynecological cancer-molecular events impricated in trophoblastic neoplasia development." The proceeding of X V FIGO. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Arima T,et al: "Association of IGF2 and H19 imprinting with choriocarcinoma development." Cancer Genet Cytogenet. 93. 39-47 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Mastuda T,et al: "Human chromosome 7 carries a putative tumor suppressor gene(s) involved in choriocarcinoma." Oncogene. 15. 2773-2781 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Wake N,et al: "Genetics of gestational trophoblastic diseases." CME Journal of Gynecologic Oncology. in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] Wake N,et al: "Involvement of IGF2 and H19 imprinting in choriocarcinoma development." FIGO,Journal. in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] Wake N,et al: "Genetics of gynecological cancer-molecular events implicated in trophoblastic neoplasia development." The proceeding of X V FIGO. in press.

    • Related Report
      1997 Annual Research Report
  • [Publications] 有馬隆博 他: "図説産婦人科VIEW" 絨毛生疾患におけるゲノムインプリンティング, 8 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] 加藤秀則 他: "癌の臨床" 発癌機序について, 10 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Arima T: "Malignant trophoblastic Neoplasms with Different Modes of Origin." Cancer Genet Cytogenet. 85. 5-15 (1995)

    • Related Report
      1996 Annual Research Report
  • [Publications] Sakamoto T: "Poor correlation with Loss of Heterozygosity on Chromosome 17p and p53 Mutations in Ovarian Cancers." Gynecol.Oncol. 65. 173-179 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kato K: "The level of ER protein expression is increased in NIH3T3 cell transformed by oncogenic K-Ras 4B : Sex Steroid Hormone Action In in vitro culture syste." Churchill Living stone Japan. 31-40 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Kato K: "Analysis of danazol action ; Endometriosis today." Parthenon Publishing. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Arima T: "Association of IGF2 and H19 imprinting with choriocarcinoma development." Cancer Genet Cytogenet. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] Kanuma T: "Alterations of the p16INK4A gene in humen ovarian cancers." Molecular Carcinogenesis. (in press).

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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