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Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells

Authors

  • R.C. Bargou
  • F. Emmerich
  • D. Krappmann
  • K. Bommert
  • M.Y. Mapara
  • W. Arnold
  • H.D. Royer
  • E. Grinstein
  • A. Greiner
  • C. Scheidereit
  • B. Doerken

Journal

  • Journal of Clinical Investigation

Citation

  • J Clin Invest 100 (12): 2961-2969

Abstract

  • The pathogenesis and etiology of Hodgkin's disease, a common human malignant lymphoma, is still unresolved. As a unique characteristic, we have identified constitutive activation of the transcription factor nuclear factor (NF)-kappaB p50-RelA in Hodgkin/Reed-Sternberg (H/RS) cells, which discriminates these neoplastic cells from most cell types studied to date. In contrast to other lymphoid and nonlymphoid cell lines tested, proliferation of H/RS cells depended on activated NF-kappaB. Furthermore, constitutive NF-kappaB p50-RelA prevented Hodgkin's lymphoma cells from undergoing apoptosis under stress conditions. Consistent with this dual function, Hodgkin's lymphoma cells depleted of constitutive nuclear NF-kappaB revealed strongly impaired tumor growth in severe combined immunodeficient mice. Our findings identify NF-kappaB as an important component for understanding the pathogenesis of Hodgkin's disease and for developing new therapeutic strategies against it.


DOI

doi:10.1172/JCI119849