| Project/Area Number |
11470211
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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 | 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 M Yamaguchi University, Graduate School of Medicine, Professor, 大学院・医学研究科, 教授 (40161343)
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| Co-Investigator(Kenkyū-buntansha) |
TSUYAMA Naohiro Yamaguchi University, Graduate School of Medicine, Researcher, 大学院・医学研究科, 助手 (10335747)
ISHIKAWA Hideaki Yamaguchi University, Graduate School of Medicine, Associate Professor, 大学院・医学研究科, 助教授 (40294623)
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| Project Period (FY) |
1999 – 2001
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| Project Status |
Completed (Fiscal Year 2001)
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| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2001: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥4,700,000 (Direct Cost: ¥4,700,000)
Fiscal Year 1999: ¥7,200,000 (Direct Cost: ¥7,200,000)
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| Keywords | myeloma / immature myeloma cells / myeloma cell differentiation / STAT1 / STAT3 / interleukin 6 / SCID mice / differentiation inducing therapy / 骨髄腫細胞 / 形質細胞分化 / CD19 / Pax-5 / Lyn / MAPK |
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| Research Abstract |
In order to establish induction system of myeloma cell differentiation and clarify intracellular signaling pathway in this induction system, we have established a human myeloma cell line, Y01 cell line, from peritoneal masses in the SCID-hIL6 transgenic (Tg) mice where human myeloma cells from the myeloma patients had been injected with agarose gel intraperitoneally. When Y01 cell lines were stimulated with IL-6, these immature myeloma cells differentiated into MPC-1 + mature myeloma cells. In response to IL-6, Y01 cell lines showed activation of STAT3 and MAPK (ERK), and activation of STAT1 was also observed only in Y01 cells, not in other IL-6-dependent myeloma cell lines. By using some inhibitors specific to the signaling molecules, it was shown that activation of MAPK was not involved in this induction of myeloma cell differentiation. These results suggested that activation of STAT1 in response to IL-6 is deeply associated with induction of myeloma cell differentiation. Furthermore, we tried to clarify the exact mechanism of intracellular signaling pathway after IL-6 stimulation, by transfecting tagged STAT1 or STAT3 gene into Hela cells. Now, these experiments are underway, and in future our study would contribute to further development of new strategy for differentiation-inducing therapy in human myelomas.
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