| Budget Amount *help |
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Outline of Final Research Achievements |
We generated conditional knockout of PU.1 by crossing Cγ1-Cre and PU.1-loxP mice. 75% of the aged knockout mice emerged diffuse large B cell lymphoma, indicating that PU.1 acts as tumor suppressor in B cells.
PU.1 expression induces cell cycle arrest and apoptosis in myeloma cells. We uncovered that PU.1 binds to IRF4 promoter and suppresses IRF4 expression. It was previously reported that IRF4 suppresses IRF7 expression by direct binding to its promoter. Indeed, we found that decreased IRF4 expression subsequently induces IRF7 expression that induces IFNβ expression. IFNβ is expressed in myeloma cells after PU.1 expression and knockdown of IFNβ partially prevent myeloma cells from apoptosis. In conclusion, PU.1 induces apoptosis in myeloma cells by suppression of IRF4 expression and subsequent up-regulation of IRF7 and IFNβ.
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