| Project/Area Number |
05807125
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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 |
Cerebral neurosurgery
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| Research Institution | Osaka University |
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Principal Investigator |
HIRAGA Shoju Osaka University, Neurosurgery, Assistant, 医学部, 助手 (40243232)
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| Co-Investigator(Kenkyū-buntansha) |
SAKOTA Saburo Osaka University, Neurology, Assistant, 医学部, 助手 (00178625)
TAKI Takuyu Osaka University, Neurosurgery, Hospital Staff, 医学部・付属病院, 医員
HAYAKAWA Toru Osaka University, Neurosurgery, Professor, 医学部, 教授 (20135700)
有田 憲生 近畿大学, 医学部, 助教授 (80159508)
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| Project Period (FY) |
1993 – 1994
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| Project Status |
Completed (Fiscal Year 1994)
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| Budget Amount *help |
¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1994: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1993: ¥900,000 (Direct Cost: ¥900,000)
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| Keywords | Immortalization / Astroglia / Glioma / p53 / Ethylnitrosourea / 悪性グリオーマ |
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| Research Abstract |
Although malignant changes from low-grade gliomas to high-grade ones have bee elucidated recently, early neoplastic changes of normal astroglia are not well understood. We reported that Cultured type 1 astroglia could be transformed in a short term by a Singe high dose of ENU and that alterations, probably missense mutations, of tumor suppressor p53 gene closely related to the cell transformation. Moreover, we established 5 immortalized type 1 astroglial cell lines. All these cell lines maintained, polygonal shape of the cell, low saturation density, regular pavement growth, slow growth, and did not have tumorigenicity in athymic mice. However, these cells showed high motility to glioma motility factor, expressed tenascin and these characteristics differed from normal astroglia.
The tumor suppressor p53 gene was extensively examined in these cell lines by various molecular biological methods. While missense mutations were demonstrated in all ENU transformed cell lines, no p53 alterations were observed in these immortalized cell lines. Thus, immortalization of the type 1 astroglia was regulated by other gene (s) than p53 or an escape from other mechanism to control cell growth and senescence. We attempted differential hybridization between normal and immortalized type 1 astroglias cDNAs. By colony screening, we obtained 200 candidate genes for immortalization and we now under investigation of these genes. Thus, this work elucidated the role of p53 in astroglial oncogenesis and further investigation on glial immortalization will provide the early genetic alteration of astroglial carcinogenesis and may lead to a new strategy for glioma therapy.
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