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Aberrantly expressed c‐Jun and JunB are a hallmark of Hodgkin lymphoma cells, stimulate proliferation and synergize with NF‐κB
Author(s) -
Mathas Stephan,
Hinz Michael,
Anagnostopoulos Ioannis,
Krappmann Daniel,
Lietz Andreas,
Jundt Franziska,
Bommert Kurt,
MechtaGrigoriou Fatima,
Stein Harald,
Dörken Bernd,
Scheidereit Claus
Publication year - 2002
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/cdf389
Subject(s) - junb , cancer research , biology , cyclin d1 , oncogene , c jun , apoptosis , lymphoma , carcinogenesis , cell growth , nf κb , cell cycle , signal transduction , transcription factor , immunology , microbiology and biotechnology , cancer , gene , biochemistry , genetics
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‐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.