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


  • S. Mathas
  • M. Hinz
  • L. Anagnostopoulos
  • D. Krappmann
  • A. Lietz
  • F. Jundt
  • K. Bommert
  • F. Mechta-Grigoriou
  • H. Stein
  • B. Dörken
  • C. Scheidereit


  • EMBO Journal


  • EMBO J 21 (15): 4104-4113


  • 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.