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

EMBO J. 2002 Aug 1;21(15):4104-13. doi: 10.1093/emboj/cdf389.

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.

Publication types

  • Comparative Study

MeSH terms

  • Cell Division
  • Cell Transformation, Neoplastic / genetics
  • Cyclin D2
  • Cyclins / biosynthesis
  • Cyclins / genetics
  • DNA, Neoplasm / metabolism
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Expression Regulation, Neoplastic / physiology*
  • Gene Expression Regulation, Neoplastic / radiation effects
  • Genes, jun*
  • Hodgkin Disease / genetics*
  • Hodgkin Disease / pathology
  • Humans
  • Lymphoma, Large B-Cell, Diffuse / genetics
  • Lymphoma, Large B-Cell, Diffuse / pathology
  • Lymphoma, Non-Hodgkin / genetics
  • Lymphoma, Non-Hodgkin / pathology
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / radiation effects
  • Mitogens / pharmacology
  • NF-kappa B / physiology*
  • Neoplasm Proteins / biosynthesis
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / physiology*
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-jun / biosynthesis
  • Proto-Oncogene Proteins c-jun / genetics
  • Proto-Oncogene Proteins c-jun / physiology*
  • Proto-Oncogene Proteins c-met / biosynthesis
  • Proto-Oncogene Proteins c-met / genetics
  • Receptors, CCR7
  • Receptors, Chemokine / biosynthesis
  • Receptors, Chemokine / genetics
  • Recombinant Fusion Proteins / physiology
  • Reed-Sternberg Cells / drug effects
  • Reed-Sternberg Cells / metabolism*
  • Reed-Sternberg Cells / radiation effects
  • Tetradecanoylphorbol Acetate / pharmacology
  • Transcription Factor AP-1 / genetics
  • Transcription Factor AP-1 / physiology*
  • Transcription, Genetic
  • Transfection
  • Tumor Cells, Cultured / drug effects
  • Tumor Cells, Cultured / metabolism
  • Tumor Cells, Cultured / radiation effects
  • Ultraviolet Rays

Substances

  • CCND2 protein, human
  • CCR7 protein, human
  • Cyclin D2
  • Cyclins
  • DNA, Neoplasm
  • MAS1 protein, human
  • Mitogens
  • NF-kappa B
  • Neoplasm Proteins
  • Proto-Oncogene Mas
  • Proto-Oncogene Proteins c-jun
  • Receptors, CCR7
  • Receptors, Chemokine
  • Recombinant Fusion Proteins
  • Transcription Factor AP-1
  • Proto-Oncogene Proteins c-met
  • Tetradecanoylphorbol Acetate