Journal
ONCOGENE
Volume 24, Issue 24, Pages 3976-3986Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/sj.onc.1208564
Keywords
Hodgkin/Reed-Sternberg cells; CD30; NF-kappa B2; IKK
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Overexpression of CD30 and constitutive nuclear factor-kappa B (NF-kappa B) activation are hallmarks of the malignant Hodgkin Reed-Sternberg (H-RS) cells. Previous investigations have demonstrated that both proliferation and survival of H-RS cells require constitutive NF-kappa B activity, which is comprised of the p50 and RekA subunits. We report here enhanced expression of NF-kappa B2/p52 and ReIB-containing NF-kappa B DNA-binding activity in Epstein-Barr virus-negative H-RS cells. Kinetic studies revealed that a proteasome inhibitor MG132 induced p100 accumulation with reduced p52 expression in H-RS cells, suggesting proteasome-dependent processing of p100. In addition, treatment with a protein synthesis inhibitor cycloheximide rapidly downregulated inhibitor of NF-kappa B (I kappa B) kinase activity in H-RS cells. We also demonstrate that overexpression of CD30 in rat fibroblasts at levels comparable to those in H-RS cells results in constitutive I kappa B kinase activation, proteasome-dependent p100 processing, and NF-kappa B-dependent cell transformation. Our results thus indicate that CD30 triggers the noncanonical NF-kappa B activation pathway, and suggest that deregulated CD30 signaling contributes to the neoplastic features of H-RS cells.
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