title: Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells.
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.
authors.affiliation: Max Delbr-uck Center for Molecular Medicine, 13122 Berlin, Germany.
authors.forename: R C
authors.initials: RC
authors.lastname: Bargou
authors.forename: F
authors.initials: F
authors.lastname: Emmerich
authors.forename: D
authors.initials: D
authors.lastname: Krappmann
authors.forename: K
authors.initials: K
authors.lastname: Bommert
authors.forename: M Y
authors.initials: MY
authors.lastname: Mapara
authors.forename: W
authors.initials: W
authors.lastname: Arnold
authors.forename: H D
authors.initials: HD
authors.lastname: Royer
authors.forename: E
authors.initials: E
authors.lastname: Grinstein
authors.forename: A
authors.initials: A
authors.lastname: Greiner
authors.forename: C
authors.initials: C
authors.lastname: Scheidereit
authors.forename: B
authors.initials: B
authors.lastname: Dörken
mesh_terms: D000818:Animals; D017209:Apoptosis; D002455:Cell Division; D002460:Cell Line; D002470:Cell Survival; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D016328:NF-kappa B / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA; D014407:Tumor Cells, Cultured
chemical_list: D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA