1997 Fiscal Year Final Research Report Summary
| Project/Area Number |
08671904
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | KYUSHU UNIVERSITY |
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Principal Investigator |
ARIMA Takahiro Medical Institute of Bioregulation Kyushu Univ.Lecturer, 生体防御医学研究所, 助手 (80253532)
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| 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)
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| Project Period (FY) |
1996 – 1997
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| Keywords | Gennomic Imprinting / RLGS-M method / IGF2-H19 / Tumor Suppressor gene / Complete mole / normal villi / choriocarcinoma |
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| 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
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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
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Research Products
(14 results)
