Constitutive nuclear factor-kappaB-RelA activation is required for proliferation and survival of Hodgkin's disease tumor cells.
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.
Bargou
R C
RC
Max Delbr-uck Center for Molecular Medicine, 13122 Berlin, Germany.
Emmerich
F
F
Krappmann
D
D
Bommert
K
K
Mapara
M Y
MY
Arnold
W
W
Royer
H D
HD
Grinstein
E
E
Greiner
A
A
Scheidereit
C
C
Dörken
B
B
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
D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D051996:Transcription Factor RelA