| Project/Area Number |
17590982
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Hematology
|
|---|
| Research Institution | Tokyo Medical and Dental University |
|---|
Principal Investigator |
TOHTU Miki Tokyo Medical and Dental University, Postgraduate School of Medicine, Lecturer, 大学院医歯学総合研究科, 講師 (90242180)
|
|---|
| Project Period (FY) |
2005 – 2006
|
| Project Status |
Completed (Fiscal Year 2006)
|
| Budget Amount *help |
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2005: ¥2,200,000 (Direct Cost: ¥2,200,000)
|
|---|
| Keywords | IRF4 / Plasmacytic differentiation / Transcription factor / Malignant Lymphoma / BCL6 / BLIMP1 |
|---|
| Research Abstract |
To investigate roles of IRF4 in B-cell development, we established germinal centre B cell-derived Burkitt's lymphoma cell lines that exogenously express IRF4. Daudi-IRF4 inducibly expressed IRF4 in the presence of doxycycline, and Raji-IRF4 constitutively expressed IRF4-estrogen receptor chimeric protein, which was activated by 4-hydroxytamoxifen. Expression or activation of IRF4 resulted in growth inhibition accompanied by accumulation of cells in G0/G1. Upregulation of the plasma cell markers CD38 and CD138 and downregulation of the germinal centre cell marker BCL6 were also observed. Furthermore, mRNAs for BCL6 and PAX5 were decreased and those for BLIMP1/PRDM1 and XBP1 were increased, which corresponds to the characteristic changes in transcription factor expression in B cells differentiating toward plasma cells. Impairment in proliferation and differentiation toward plasma cells induced by IRF4 were not inhibited by enforced expression of BCL6. These results suggest that IRF4 inhibits cell cycle progression of germinal centre B cell-derived Burkitt's lymphoma cells and induces its terminal differentiation toward plasma cells through mechanisms independent of BCL6 downregulation.
|
