2000 Fiscal Year Final Research Report Summary
Role of NF2 tumor suppressor gene promoter in the tumorigenesis
| Project/Area Number |
11671371
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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 | Kagoshima University (2000)
Kumamoto University (1999) |
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Principal Investigator |
TAKESHIMA Hideo University Hospital Faculty of Medicine, Kagoshima university, Assistant Professor, 医学部・附属病院, 講師 (70244134)
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| Co-Investigator(Kenkyū-buntansha) |
KURATSU Jun-ichi Faculty of Medicine, Kagoshima university, Professor, 医学部, 教授 (20145296)
USHIO Yukitaka Faculty of Medicine, Kumamoto University, Professor, 医学部, 教授 (20028583)
NISHI Toru University Hospital Faculty of Medicine, Kumamoto University, Research Associate, 医学部・附属病院, 助手 (00264309)
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| Project Period (FY) |
1999 – 2000
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| Keywords | NF2 / gene / promoter / cloning / luciferase / methylation |
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| Research Abstract |
Background : Although mutational inactivation and allelic loss in the NF2 gene appear to be causal events in the majority of vestibular schwannomas, involvement of another potentially important mechanism, transcriptional inactivation, has not been investigated. Results : We cloned and functionally characterized the 5'-flanking region of the human NF2 gene and identified the molecular mechanisms that regulate NF2 expression. Luciferase assay and site-directed mutagenesis demonstrated that a 70-base pair (bp) region (-591 to -522 bp from the translation start site) was essential for the basic expression of the NF2 gene. Gel mobility shift assay indicated recognition by nuclear protein(s) of the unusually long (〜66 bp) sequences in this region. Recognition was inhibited by either mutation of the binding core sequence or by methylation of three CpG sites. Point mutations at these CpG sites significantly decreased promoter activity, suggesting the importance of these sites. In 14 of 23 vestibular schwannomas, these 3 CpG sites within this region were methylated in a site-specific manner and the methylation status was consistent with the expression of NF2 mRNA.Conclusions : Suppressed expression by aberrant methylation or mutation of the promoter elements could be an alternative mechanism for inactivation of the NF2 gene.
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[Publications] Yamamoto, K., Takeshima, H., Hamada, K., Nakao, M., Kino, T., Nishi, T., Kochi, M., Kuratsu, J., Yoshimura, T., and Ushio, Y.: "Cloning and functiional characterization of the 5'-flanking region of the human monocyte chemoattractant protein-1 receptor (CCR2) gene.-Essential role of 5'-untranslated region in tissue specific expression."J.Biol.Chem.. 274. 4646-4654 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Takeshima, H., Kino, T., Nishi, T., Yamamoto, K., Kimura, T., Saito, T., Kochi, M., and Ushio, Y.: "Identification and characterization of the cis-regulatory element in NF2 gene promoter that is inactivated by methylation in vestivular schwannomas."Neuro-Oncology. 1. S76 (1999)
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「研究成果報告書概要(欧文)」より
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[Publications] Kino, T., Takeshima, H., Nishi, T., Yamamoto, K., Nakao, M., Saito, Y., Kochi, M., Kuratsu, J., Saya, H., and Ushio, Y.: "Identification of the cis-acting region in the NF2 gene promoter as a potential target formutation and methylation-dependent silencing in schwannoma."Genes to Cells. 6. 1-15 (2001)
Description
「研究成果報告書概要(欧文)」より
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