Constitutive nuclear factor-κB-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)-kappa B 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-kappa B, Furthermore, constitutive NF-kappa B 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-kappa B revealed strongly impaired tumor growth in severe combined immunodeficient mice, Our findings identify NF-kappa B as an important component for understanding the pathogenesis of Hodgkin's disease and for developing new therapeutic strategies against it.