title: Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappa B.
abstract: AP-1 family transcription factors have been implicated in the control of proliferation, apoptosis and malignant transformation. However, their role in oncogenesis is unclear and no recurrent alterations of AP-1 activities have been described in human cancers. Here, we show that constitutively activated AP-1 with robust c-Jun and JunB overexpression is found in all tumor cells of patients with classical Hodgkin's disease. A similar AP-1 activation is present in anaplastic large cell lymphoma (ALCL), but is absent in other lymphoma types. Whereas c-Jun is up-regulated by an autoregulatory process, JunB is under control of NF-kappa B. Activated AP-1 supports proliferation of Hodgkin cells, while it suppresses apoptosis of ALCL cells. Furthermore, AP-1 cooperates with NF-kappa B and stimulates expression of the cell-cycle regulator cyclin D2, proto-oncogene c-met and the lymphocyte homing receptor CCR7, which are all strongly expressed in primary HRS cells. Together, these data suggest an important role of AP-1 in lymphoma pathogenesis.
authors.affiliation: Max-Delbrück-Center for Molecular Medicine and Universitätsklinikum Charité, Robert-Rössle-Klinik, Humboldt University, Lindenberger Weg 80, D-13125 Berlin.
authors.forename: Stephan
authors.initials: S
authors.lastname: Mathas
authors.forename: Michael
authors.initials: M
authors.lastname: Hinz
authors.forename: Ioannis
authors.initials: I
authors.lastname: Anagnostopoulos
authors.forename: Daniel
authors.initials: D
authors.lastname: Krappmann
authors.forename: Andreas
authors.initials: A
authors.lastname: Lietz
authors.forename: Franziska
authors.initials: F
authors.lastname: Jundt
authors.forename: Kurt
authors.initials: K
authors.lastname: Bommert
authors.forename: Fatima
authors.initials: F
authors.lastname: Mechta-Grigoriou
authors.forename: Harald
authors.initials: H
authors.lastname: Stein
authors.forename: Bernd
authors.initials: B
authors.lastname: Dörken
authors.forename: Claus
authors.initials: C
authors.lastname: Scheidereit
mesh_terms: D002455:Cell Division; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004273:DNA, Neoplasm / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D016758:Genes, jun; D006689:Hodgkin Disease / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000528:radiation effects; D008934:Mitogens / Q000494:pharmacology; D016328:NF-kappa B / Q000502:physiology*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D019859:Proto-Oncogene Proteins c-met / Q000096:biosynthesis / Q000235:genetics; D054400:Receptors, CCR7; D019707:Receptors, Chemokine / Q000096:biosynthesis / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000502:physiology; D016539:Reed-Sternberg Cells / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D018808:Transcription Factor AP-1 / Q000235:genetics / Q000502:physiology*; D014158:Transcription, Genetic; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: C080336:CCND2 protein, human; C515370:CCR7 protein, human; D056742:Cyclin D2; D016213:Cyclins; D004273:DNA, Neoplasm; C000715470:MAS1 protein, human; D008934:Mitogens; D016328:NF-kappa B; D009363:Neoplasm Proteins; D000090063:Proto-Oncogene Mas; D016755:Proto-Oncogene Proteins c-jun; D054400:Receptors, CCR7; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins; D018808:Transcription Factor AP-1; D019859:Proto-Oncogene Proteins c-met; D013755:Tetradecanoylphorbol Acetate