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  • The EMBO Journal (2002) 21, 4104 - 4113
  • doi:10.1093/emboj/cdf389

Aberrantly expressed c-Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF-kappaB

Stephan Mathas1,2, Michael Hinz1, Ioannis Anagnostopoulos3, Daniel Krappmann1, Andreas Lietz1, Franziska Jundt1,2, Kurt Bommert1, Fatima Mechta-Grigoriou4, Harald Stein3, Bernd Dörken1,2 and Claus Scheidereit1

  1. Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Stras zlige 10, D-13125 Berlin, Germany
  2. Universitätsklinikum Charité, Robert-Rössle-Klinik, Humboldt University, Lindenberger Weg 80, D-13125 Berlin, Germany
  3. Institute for Pathology, Universitätsklinikum Benjamin Franklin, Free University, Hindenburgdamm 30, 12200 Berlin, Germany
  4. Unité des Virus Oncogènes, URA CNRS 1644, Institut Pasteur, 28 Rue du Dr Roux, 75724 Paris cedex 15, France

Correspondence to:

Claus Scheidereit, E-mail: scheidereit@mdc-berlin.de

Received 30 January 2002; Accepted 3 June 2002; Revised 28 May 2002

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-kappaB. Activated AP-1 supports proliferation of Hodgkin cells, while it suppresses apoptosis of ALCL cells. Furthermore, AP-1 cooperates with NF-kappaB 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.

  • Keywords:

    • lymphoma,
    • MAPK,
    • metastasis,
    • oncogenesis,
    • target genes