Genetic approaches to explore the mechanism of human endometrial carcinogenesis
| Project/Area Number |
61570776
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Hokkaido University |
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Principal Investigator |
SATO Hiroshi Hokkaido University School of Medicine, 医学部, 助手 (90178765)
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| Co-Investigator(Kenkyū-buntansha) |
WAKE Norio Hokkaido University Medical Hospital, 医学部附属病院, 講師 (50158606)
一戸 喜兵衛 北海道大学, 名誉教授 (90073783)
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| Project Period (FY) |
1986 – 1988
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| Project Status |
Completed (Fiscal Year 1988)
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| Budget Amount *help |
¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1988: ¥400,000 (Direct Cost: ¥400,000)
Fiscal Year 1987: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1986: ¥1,600,000 (Direct Cost: ¥1,600,000)
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| Keywords | Endometrial Carcinoma / cell hybridization / Microcell mediated single chromosome transfer / Tumorigenesis / 癌抑制遺伝子 / 造腫瘍性 / 癌遺伝子 / Endometrial Carcinoma / Chromosome / abnormality involving 1q / Cell fusion / tumorigenecity |
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| Research Abstract |
Two kinds of clones were isolated successfully from the HHUA 95 cells which derived from the human well differentiated adenocarcinoma of endometrium, with the 6-thioguanine (6-TG) selection and the pSV2-neo transfection. The one was resistant to the 6-TG(6-TG^r 95) and the other was resistant both to the 6-TG and the neomycin (6-TG^r-neo^r 95). Karyotypes of these three kinds of cells were normal even if random chromosome abnormalities were observed in some cells. The neo genes were integrated at least into the 18 kinds of chromosomes of the 6-TG^r -neo^r 95 cells.
Two type of cell fusion were performed ; the one was the hybridization betweep 6-TG^r 95 cells and normal human fibroblasts (HF) and the other was one between 6-TG^r-neo^r 95 and human choriocarcinoma cells (CC1). Tumorigenicity of both hybrid cells were completely suppressed. Complementation for genetic lesions given by the cell hybridization was assumed to be responsible for the suppression of tumorigenicity. These results
… More
suggested that genetic losses played an essential role in the evolution of the malingant phenotype and the data obtained from the endometrial carcinoma could not be available directly for the understanding of suppression mechanisms of choriocarcinoma.
Alterations of various transformed phenotypes of a human uterine endometrial carcinoma cell line HHUA following introduction of various normal human chromosomes were examined. We first constructed mouse A9 clones which contained a single human chromosome tagged with pSV2-neo, i.e., #1, #6, #9, #11, and #19, and transferred each chromosome to HHUA cells via microcell fusion. A large proportion of G418 resistant colonies which were formed by microcell fusion with microcells only from A9 cells containing chromosome 1 senesced at an early passage. The tumorigenicity of HHUA was completely suppressed by the introduction of either chromosome 1, 6 or 9. Particularly, the HHUA microcell hybrids with the introduction of the chromosome 1 also showed concurrent alteration in other transformed phenotypes, e.g., flat morphology, decrements of saturation density and growth in vitro. These results suggest that multiple genes may be involved in recessive and/or dosage mechanisms for the malignant transformation at different steps. Less
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Report
(4 results)
Research Products
(29 results)
