CONSTITUTIVE NUCLEAR FACTOR-KAPPA-B-RELA ACTIVATION IS REQUIRED FOR PROLIFERATION AND SURVIVAL OF HODGKINS-DISEASE TUMOR-CELLS

The pathogenesis and etiology of Hodgkin's disease, a common human mal ignant lymphoma, is still unresolved, As a unique characteristic, we h ave identified constitutive activation of the transcription factor nuc lear factor (NF)-kappa B p50-RelA in Hodgkin/Reed-Sternberg (H/RS) cel ls, which discriminates these neoplastic cells from most cell types st udied to date, In contrast to other lymphoid and nonlymphoid cell line s tested, proliferation of H/RS cells depended on activated NF-kappa B , Furthermore, constitutive NF-kappa B p50-RelA prevented Hodgkin's ly mphoma cells from undergoing apoptosis under stress conditions, Consis tent with this dual function, Hodgkin's lymphoma cells depleted of con stitutive nuclear NF-kappa B revealed strongly impaired tumor growth i n severe combined immunodeficient mice, Our findings identify NF-kappa B as an important component for understanding the pathogenesis of Hod gkin's disease and for developing new therapeutic strategies against i t.