Stephan Mathas

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

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 Hodgkins 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‐κB. Activated AP‐1 supports proliferation of Hodgkin cells, while it suppresses apoptosis of ALCL cells. Furthermore, AP‐1 cooperates with NF‐κB 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.