| Project/Area Number |
09470362
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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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 |
WAKE Norio Medical Institute of Bioregulation, Kyushu Univ., Professor, 生体防御医学研究所, 教授 (50158606)
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| Co-Investigator(Kenkyū-buntansha) |
NISHIDA Jun-ichi Medical Institute of Bioregulation, Kyushu Univ., Research Associate, 生体防御医学研究所, 助手 (40264113)
KATO Kiyoko Medical Institute of Bioregulation, Kyushu Univ., Assistant Professor, 生体防御医学研究所, 講師 (10253527)
KATO Hidenori Medical Institute of Bioregulation, Kyushu Univ., Assistant Professor, 生体防御医学研究所, 講師 (60214392)
MATSUDA Takao Medical Institute of Bioregulation, Kyushu Univ., Research Associate, 生体防御医学研究所, 助手 (10304825)
有馬 隆博 九州大学, 生体防御医学研究所, 助手 (80253532)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥15,400,000 (Direct Cost: ¥15,400,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 1997: ¥9,500,000 (Direct Cost: ¥9,500,000)
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| Keywords | endometrial cancer / a tumor suppressor gene on 1q / cell senescence / Ras / ER / DPC4 / DOC / cyclin G / tumor supppressor gene on 1q / 癌抑制遺伝子 / 子宮体癌 / 1番染色体 / 微小核融合 / 変異型K-Ras / エストロゲンリセプター / 形質転換 / 変異型K・Ras |
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| Research Abstract |
1. Identification of an endometrial cancer suppressor gene locus : The gene located chromosome 1q has an ability to induce senescence in endometrial cancer cells. By introducing a del 1q chromosome that has incurred an interstitial deletion of approximately 63 cM or subchromosomal transferable fragments derived from the 1q into the endometrial cancer cells, we identified the localization of a target gene within 1q31-ter. In addition, we analyzed LOH on 1q using 60 sample of endometrial cancers and narrowed down the localization with 1q42.
2. Contribution of ER to Ras mediated transformation. Mutant K-ras protein had an ability to induce expression of ER protein (3-fold) that functioned as a transcription factor. Reconstituted cells that had enhanced ER activities were tumorigenic but the cells with lower ER activities were nontumorigenic. Suppression of ER activities resulted in the loss of tumorigenicity in the cells transformed by mutant k-ras.
3. Both DPC4 and DOC genes targeted by 18q LOH in endometrial cancers. : 18qLOH is frequent in endometrial cancers. By making a detailed deletions map on 18q, we found that deletions targeted both DPC4 and DOC genes. Mutations of the DPC4 promoter regions in the remaining allele resulted in the suppression of DPC4 gene activities. In turn, transfection of DOC cDNA resulted in the suppression of tumorigenicity or the induction of apoptosis in endometrial cancer cells. A DOC gene functions as a tumor suppressor gene by inducing apoptosis of endometrial cells.
4. Function of p53-dependent cyclin G : Dox treatment induced p53 accumulation, p21 and cyclin G transcription, that resulted in G2/M arrest of cells. In turn, NaB induced p53 accumulation and p21 transcription but not cyclin G transcription, that resulted in G1 arrest of cells. Suppression of cyclin G expression corresponded to the release of cells from G2/M. Overexpression of cyclin G reverted the cell susceptible to apoptosis.
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