title: CD30 Induces Heat Shock Protein 90 and Signal Integration in Classic Hodgkin Lymphoma Cells.
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.
authors.affiliation: Department of Hematology, School of Medicine, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Mariko
authors.initials: M
authors.lastname: Watanabe
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Kazumi
authors.initials: K
authors.lastname: Nakano
authors.affiliation: Department of Dermatology and Skin Surgery, Boston University School of Medicine, Roger Williams Medical Center, Providence, Rhode Island.
authors.forename: Marshall E
authors.initials: ME
authors.lastname: Kadin
authors.affiliation: Department of Hematology, School of Medicine, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan.
authors.forename: Masaaki
authors.initials: M
authors.lastname: Higashihara
authors.affiliation: Laboratory of Tumor Cell Biology, Department of Medical Genome Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo, Japan.
authors.forename: Toshiki
authors.initials: T
authors.lastname: Watanabe
authors.affiliation: Department of Hematology, School of Medicine, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan; Division of Hematology, Department of Laboratory Sciences, School of Allied Health Sciences, Kitasato University, Minami-ku, Sagamihara, Kanagawa, Japan. Electronic address: rhorie@med.kitasato-u.ac.jp.
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Horie
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D045744:Cell Line, Tumor; D004268:DNA-Binding Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D018869:Heat-Shock Response / Q000235:genetics; D006689:Hodgkin Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D017730:Ki-1 Antigen / Q000378:metabolism*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000378:metabolism; D008954:Models, Biological; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020218:Response Elements / Q000235:genetics; D050791:STAT Transcription Factors / Q000378:metabolism; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D018841:HSP90 Heat-Shock Proteins; D000076249:Heat Shock Transcription Factors; D017730:Ki-1 Antigen; D016328:NF-kappa B; D050791:STAT Transcription Factors; D014157:Transcription Factors; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D020794:Receptor Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases