| Project/Area Number |
10670952
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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 |
ISHIKAWA Hideaki Yamaguchi University, School of Medicine, Associate Professor, 医学部, 助教授 (40294623)
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| Co-Investigator(Kenkyū-buntansha) |
FUJII Ryuichi Yamaguchi University, School of Medicine, Research Associate, 医学部, 助手 (30264401)
KAWANO Michio Yamaguchi University, School of Medicine, Professor, 医学部, 教授 (40161343)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 1999: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1998: ¥1,900,000 (Direct Cost: ¥1,900,000)
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| Keywords | myeloma / CD19 / IL-6 / STAT3 / ERK1 / 2 / cell proliferation / signal transduction / SCID mice / CD45 / MAPK |
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| Research Abstract |
Plasma cells do express CD19, whereas myeloma cells lack its expression. Several stable transfectants of human myeloma cell line KMS5 expressing either wild type or mutant of the CD19 genes which encodes the cytoplasmic region-truncated protein were established. Compared with KMS5 cells expressing the CD19 mutants as a control, the proliferation in vitro, tumorigenicity in SCID mice and anchorage-independent growth in soft agar were markedly reduced in CD19-expressing cells. These results indicate that the CD19 molecule seems to regulate neagtively the proliferation of KMS5 cells.
Stable transfectants of the CD19 genes into other myeloma cell line U266 were also obtained. The in vitro proliferation in the absence of interleukin-6 (IL-6) of U266 cells expressing CD19 was slower than that of control, consistent with the result obtained from the IL-6-independent cell line KMS5. The CD19-expressing U266 cells, however, proliferated rapidly in response to IL-6 relative to control. Signal transducers and activators of transcription 3 (STAT3) and extracellular signal-regulated kinase 1/2 (ERK1/2) were activated following to IL-6 stimulation in U266 cells. Both activation in response to IL-6 seemed to be stronger in CD19ィイD1+ィエD1U266 than in control U266 cells. These results suggest that CD19 inhibits cell proliferation independent on IL-6, whereas it enhances the IL-6-promoted proliferation of myeloma cells. Further studies investigating how CD19 invoves the IL-6 signaling pathways will be necessary.
Non-tumorigenic U266 cells (10ィイD15ィエD1 cells) could be transplanted into the abdomen of SCID mice by pre-injection of agarose gels. The effect of CD19 on cell proliferation observed in vitro should be examined in vivo by using the CD19-transfected U266 cells.
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