2006 Fiscal Year Final Research Report Summary
Comprehensive analyses of Epstein-Barr virus(EBV) -dependent cellular gene expressions responsible for the viral oncogenesis
| Project/Area Number |
17590418
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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 |
Virology
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| Research Institution | Kochi University |
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Principal Investigator |
IMAI Shosuke Kochi University, Department of microbiology, Professor (60232592)
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| Co-Investigator(Kenkyū-buntansha) |
KURODA Masayuki Kochi University, Department of Microbiology, Instructor (00253005)
MATUMOTO Kenji National Research Institute for Child Health & Development, Department of Allergy & Immunology, Laboratory Head (60181765)
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| Project Period (FY) |
2005 – 2006
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| Keywords | Epstein-Barr virus(EBV) / oncogenic genes / microarray / T / NK cell tumor / epithelial tumor / cytokines |
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| Research Abstract |
The aim of this study was to identify the cellular genes closely related to or responsible for Epstein-Barr virus (EBV)-induced oncogenesis in naturally EBV-positive T/NK and epithelial tumor cells, by utilizing a unique molecule capable of eradicating EBV episomes from cells, i.e., dominant-negative EBNA1 (DNE1; Mol. Ther., 11(4):578-90, 2005). We prepared isogenic pairs of EBV-positive and-negative cell lines by DNE1 transduction and compared their malignant grade. Concomitantly alterations of cellular gene expression in those cell pairs were comprehensively assessed with the multi-cytokine assay and GeneChip microarray system, thereby elucidating the role(s) of EBV in malignant conversion. The results obtained are as follows.
1. Adenovirus vector-mediated transduction of our DNE1 successfully eradicated EBV episomes from the majority of naturally EBV-positive T/NK lymphoma and epithelial tumor cell lines in a few days.
2. The EBV-lost T/NK cells produced by DNE1 showed a striking suppression of their malignant phenotypes, such as prolongation of doubling time and loss of anchorage-independent growth potential, compared with parental EBV-harboring T/NK tumor cells. In a part of the EBV-lost T/NK cells, loss of viral genome also brought about cell death.
3. The EBV-lost T/NK cells showed significantly decreased production of some cytokines, such as interleukin-9, compared with the parental EBV-harboring T/NK tumor cells. Conversely, the production levels of a few other cytokines were also found to be upregulated in the EBV-lost T/NK cells.
These results indicate that the EBV-dependent malignant phenotypes in T/NK cells and perhaps also in epithelial cells, as in B-cell malignancy, are associated at least partly with upregulation (i.e., the autocrine mechanism) and/or downregulation of certain cytokine genes. We are planning to explore precisely the mechanisms of cytokine gene control and specific effects on EBV oncogenesis.
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Research Products
(34 results)
