| Project/Area Number |
03454399
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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) |
IMAMURA Toshiro Medical Institute of Bioregulation Kyusyu Univ., Assistant, 生体防御医学研究所, 助手 (10221095)
MIYAMOTO Shingo Medical Institute of Bioregulation Kyushu Univ., Assistant, 生体防御医学研究所, 助手 (40209945)
KATO Hidenori Medical Institute of Bioregulation Kyushu Univ., Assistant, 生体防御医学研究所, 助手 (60214392)
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| Project Period (FY) |
1991 – 1992
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| Project Status |
Completed (Fiscal Year 1992)
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| Budget Amount *help |
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1992: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1991: ¥4,400,000 (Direct Cost: ¥4,400,000)
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| Keywords | Endometrial carcinoma / genetic events / K-ras gene mutation / tumor suppressor genes / microcell fusion / LOH / 遺伝子クロ-ニング |
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| Research Abstract |
The present study was undertaken to disclose the involvement of multiple genetic events in neoplastic transformation of human endometrium. Microcell mediated a chromosome 1 transfer into endometrial carcinoma cells associated with the suppression of tumorigenecity and in vitro growth properties, suggesting the presence of tumor suppressor gene(s) on chromosome 1. Loss of chromosome 4 from the nontumorigenic whole cell hybrids between endometrial carcinoma cells and normal fibroblasts correlated with the recovery of tumorigenecity. In addition to these results, comprehensive analyses of allelic losses and point mutations of ras genes disclosed that at least 3 genetic events, including 18q, 17p deletions, and point mutations at codon 12 of the K-ras gene, were implicated in the development of endometrial carcinomas. Likely targets for these allelic losses were the DCC gene and the p53 gene sequences, respectively. The involvement of putative suppressor gene(s) locating on chromosome 1 in formation of hyperplastic focus with cellular atypism may be speculated by alterations of transformed phenotypes in the microcell hybrid containing an extra copy of chromosome 1. The genetic events implicating K-ras gene mutatin, loss of DCC gene and chromosome 4 deletion corresponded to the transition from hyperplasia to neoplasia. The p53 gene mutations seemed to be implicated in the progression following the development of fully malignant tumors.
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