RRC ID 61413
著者 Watanabe M, Nakano K, Kadin ME, Higashihara M, Watanabe T, Horie R.
タイトル CD30 Induces Heat Shock Protein 90 and Signal Integration in Classic Hodgkin Lymphoma Cells.
ジャーナル Am J Pathol
Abstract Previous studies report deregulation of multiple signaling pathways in classic Hodgkin lymphoma (cHL) cells. However, the mechanisms of how these pathways are integrated are not fully understood. Herein, we show involvement of cHL hallmark antigen CD30 in this process. CD30 facilitates phosphorylation of heat shock factor 1, activates heat shock promoter element, and induces heat shock protein (HSP) 90. CD30 repression and subsequent inhibition of HSP90 suppresses NF-κB, extracellular signal-regulated kinase, 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. We also show that CD30 induces HSP90 through phosphorylation of heat shock factor 1 via c-Jun N-terminal kinase in cHL cells. Although anaplastic large-cell lymphoma (ALCL) also is associated with CD30 overexpression, our experiments reveal that HSP90 induction in ALCL-bearing nucleophosmin-anaplastic lymphoma kinase (ALK) does not depend on CD30 but instead on ALK via c-Jun N-terminal kinase. 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.
巻・号 187(1)
ページ 163-175
公開日 2017-1-1
DOI 10.1016/j.ajpath.2016.09.007
PII S0002-9440(16)30410-2
PMID 27870927
MeSH Anaplastic Lymphoma Kinase Cell Line, Tumor DNA-Binding Proteins / metabolism Extracellular Signal-Regulated MAP Kinases / metabolism HSP90 Heat-Shock Proteins / metabolism* Heat Shock Transcription Factors Heat-Shock Response / genetics Hodgkin Disease / metabolism* Hodgkin Disease / pathology Humans JNK Mitogen-Activated Protein Kinases / metabolism Ki-1 Antigen / metabolism* Lymphoma, Large-Cell, Anaplastic / metabolism Models, Biological NF-kappa B / metabolism Phosphorylation Proto-Oncogene Proteins c-akt / metabolism Receptor Protein-Tyrosine Kinases / metabolism Response Elements / genetics STAT Transcription Factors / metabolism Signal Transduction* Transcription Factors / metabolism
IF 3.491
リソース情報
ヒト・動物細胞 Ba/F3(RCB0805)