| Project/Area Number |
12671367
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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 |
Cerebral neurosurgery
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| Research Institution | Saga Medical School |
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Principal Investigator |
SHIRAISHI Tetsuya Saga Medical School, Neurosurgery, Instructor, 医学部, 講師 (70206275)
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| Co-Investigator(Kenkyū-buntansha) |
TABUCHI Kazuo Saga Medical School, Neurosurgery, Professor, 医学部, 教授 (50116480)
萩原 直司 佐賀医科大学, 医学部, 助手 (90281203)
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| Project Period (FY) |
2000 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | p161NK4a / p14ARF / p53 / cytoplasmic accumulation / nuclear localizing signal / mutation / glioma / 膠芽腫 / p16 / brain tumor / p14INK4a / p14 |
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| Research Abstract |
The expression of p16INK4a is altered in 60 - 80 % of malignant gliomas due to homozygous deletion, point mutation or DNA methylation. The authors tried to elucidate the alteration of another INK4a gene products, p14ARF, in malignant gliomas. p14ARF binds directly to MDM2, preventing the digestion of p53 by ubiquitine. The alteration of p14ARF is supposed to promote tumor progression through negative regulation of p53 in malignant gliomas. The expression of p16INK4a, p14ARF, MDM2 and p53 was examined by immunohistochemistry in 93 malignant gliomas [39 anaplastic astrocytomas (AA), 54 glioblastomas (GB)]. Southern blot analysis and DNA sequence of INK4a gene were performed for selected cases. p16INK4a expression was deficient in 23/39 (59.0 %) AAs and 27/54 (50.0 %) GBs, respectively. All of p16INK4a deficient cases were also deficient for p14ARF. Cytoplasmic accumulation of p!6INK4a was detected in 5/39 (12.8 %) AAs and 17/54 (31.5 %) GBs.
Point mutation was detected in 2 cases with cytoplasmic p16INK4a. Among 22 cases with cytoplasmic p16INK4a, p14ARF was also accumulated in cytoplasm of 2 cases, but deficient 20 cases. p16INK4a and p14ARF ware positive in nuclei of 11/39 (28.2 %) AAs and 10/54 (18.5 %) GBs. Alteration of INK4a gene caused both p16INK4a and p14ARF deficiency in malignant gliomas. Besides homozygous deletion of INK4a gene, alternative negative regulating mechanism of p16INK4a might be present.
Cytoplasmic accumulation due to point mutation of INK4a gene could be one of the alternative mechanisms for inactivation of p16INK4a and p14ARF in malignant gliomas.
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