2002 Fiscal Year Final Research Report Summary
Molecular biologic and pathologic study of Epstein-Barr virus infected lymphepithalial carcinomas in salivary gland
| Project/Area Number |
12576024
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 海外学術 |
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| Research Field |
病態科学系歯学(含放射線系歯学)
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| Research Institution | NIIGATA UNIVERSITY |
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Principal Investigator |
SAKU Takashi Niigata University, Graduate School of Medical and Dental Sciences, Professor, 大学院・医歯学総合研究科, 教授 (40145264)
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| Co-Investigator(Kenkyū-buntansha) |
SUZUKI Makoto Niigata University, University Dental Hospital, Lecturer, 歯学部附属病院, 講師 (50107778)
OUSHIRO Kazufumi Niigata University, Graduate School of Medical and Dental Sciences Associate Professor Graduate School of Medical and Dental Sciences Assistant University Dental Hospital Lecturer Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (50332648)
CHENG Jun Niigata University, Graduate School of Medical and Dental Sciences, Associate Professor, 大学院・医歯学総合研究科, 助教授 (40207460)
IDA Hiroko Niigata University, Graduate School of Medical and Dental Sciences, Assistant, 大学院・医歯学総合研究科, 助手 (60293213)
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| Project Period (FY) |
2000 – 2002
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| Keywords | lymphoepithelial carcinoma / salivary gland tumor / EBV / LMP1 gene / gene polymorphism / cell culture / PCR / carcinogenetic mutations |
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| Research Abstract |
A total 180 cases of salivary gland lymphoepithelial carcinoma (LEC) were col lected from Russia-Asian countries. Their paraffin blocks of surgical materials were obtained for imunohistochemistry, in-situ hybridization and DNA extraction
Immunohistochemically, about 50% of the cases showed positive signals for LMP1 gene products, and 100% of them had EBER-1 RNA signals in tumor cells' nuclei, which suggested a definite EBV infection among salivary LEC cases. From 40 cases of them, the C-terminus of the LMP1 gene was PCR-amplified and direct-sequenced. The results indicated that there were at least two different strains of EBV harboring in salivary LEC and that there were many mutational events in them including the characteristic 30 by delefion. From 12 cases of them, the complete sequence for, the LMP1 gene were obtained, and many and new mutations in addition to those which were already found in nasapharyngeal LEC. The promoter region of the LMP1 gene was also analyzed from 20 cases o
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f them, and all of the cases shared common mutational events in regions which were expected to be associated with transcription factors
One of the complete sequence obtained as mentioned above were cloned into an expression vector and the constructs were transfected into 293T cells to determine their effectd on the activation of NFkB pathways as well as cell growth. The transfected cells showed significant elevation of NFkB activities and suppressed cell growth, which were also seen in cells transfected with vectors with nasopharyngeal CAO or prototype B95-8. The results indicated that the expression of LMP1 affects transcritption activities in LEC cells but that the overall mutaions found in the present study were not always reasons for the tumorigenesis
Primary cultures for salivary LECs were tried many times. However, the cells were hard to maintain. One of them are growing now and they were characterized by immunofluorescence and PCR to be epithelial and EBV infected
The results obtained as above has given us a new insight for EBV roles in the pathogenesis of salivary LEC. To this end, it is necessary to carry out further investigations on molecular functions of EBV oncogenes Less
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[Publications] Saku T, Cheng J, Jen KY, Tokunaga M, V J, Zhang W, Liu A, Wu L, Lu Y, Zhou Z, Li Y, Li R, Ouyang J, Yang L, Yu S, Lou T, Wang S, Lin D, Rao H, Lin H, Sderk P, Chen Z, Cai C, Kim H, Hong S, Turbin D, Petrovichev N, Gurtsevitch V: "Epstein-Barr virus infected lymphepitehlial carcinomas of the salivary glandin the Russian-Asian area : a clinicopathologic study of 160 cases"Archiv Pathol. 65(2). 35-39 (2003)
Description
「研究成果報告書概要(欧文)」より
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