| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Outline of Final Research Achievements |
Although classical Hodgkin lymphoma (cHL) cells bear deregulation of multiple signaling pathways, the mechanisms of how these pathways are integrated are not fully understood. We show involvement of CD30 in this process. CD30 facilitates phosphorylation of heat shock protein factor (HSF)1 and induces heat shock protein (HSP) 90 via JNK. CD30 repression and subsequent inhibition of HSP90 suppresses NF-κB, ERK/MAPK, AKT, and STAT pathways in cHL cell lines. Thus CD30 mediated induction of HSP90 appears to serve as a central hub for integration of intracellular signaling in cHL cells. Although anaplastic large cell lymphoma (ALCL) is associated with CD30 overexpression, our experiments reveal that HSP90 induction in ALCL bearing NPM- ALK does not depend on CD30 but instead on ALK via JNK. Together these results highlight a novel role for CD30 in mediating integration of signaling pathways of cHL cells while being replaced in this function by ALK in ALCL cells.
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