| Project/Area Number |
09671115
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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 |
Hematology
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| Research Institution | Yamaguchi University |
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Principal Investigator |
KAWANO Michio Faculty of Medicine, Yamaguchi University Professor, 医学部, 教授 (40161343)
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| Co-Investigator(Kenkyū-buntansha) |
ISHIKAWA Hideaki Faculty of Medicine, Yamaguchi University Associate Professor, 医学部, 助教授 (40294623)
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥3,000,000 (Direct Cost: ¥3,000,000)
Fiscal Year 1998: ¥800,000 (Direct Cost: ¥800,000)
Fiscal Year 1997: ¥2,200,000 (Direct Cost: ¥2,200,000)
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| Keywords | Myeloma / Pax-5 / Methylation / CD19 / Gene transfer / Transcription factor / Myeloma cell / SCID mouse |
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| Research Abstract |
In order to clarify the mechanism of oncogenesis of human myeloma, we isolated and cloned 5' upstream region of human Pax-5 gene that is specifically lost in myeloma cells. We investigated the structural abnormality of Pax-5 gene in human myeloma cell lines and primary myeloma cells from myeloma patients. Also, we examined the biological significance of loss of CD19 in myeloma cell lines by introduction of CD19 gene expression into these cell lines. Neither rnyeloma cell lines nor primary myeloma cell showed any structural abnormality of Pax-5 gene including 5' upstream region. However, within 4 kb upstream region of Pax-5 gene, CpG sites were hypermethylated in myeloma ceIl lines and primary myeloma cells compared with Pax-5-positive B cell lines. Furthermore, treatment of myeloma cell lines with azadeoxycytidine recovered their expression of Pax- 5 gene. These results suggest that loss of Pax-5 expression in myeloma cells may be derived from hypermethylation of upstream regulatory region of Pax-5 gene. Another interesting finding was obtained transfection of CD19 gene into myeloma cell lines showed marked reduction of their proliferation both in vitro and in SCID mice. This suggests that loss of CD19 expression in myeloma cells is not merely the result from loss of Pax-5 gene expression but makes sense of acquisition of growth advantage during oncogenesis. In conclusion, in this project, we obtained fruitful results that altered expression of P ax-5 gene is closely associated with onco genesis of human myeloma.
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