Aberrant NF-kappaB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts.
Overexpression of CD30 and constitutive nuclear factor-kappaB (NF-kappaB) 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-kappaB activity, which is comprised of the p50 and RelA subunits. We report here enhanced expression of NF-kappaB2/p52 and RelB-containing NF-kappaB 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-kappaB (IkappaB) 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 IkappaB kinase activation, proteasome-dependent p100 processing, and NF-kappaB-dependent cell transformation. Our results thus indicate that CD30 triggers the noncanonical NF-kappaB activation pathway, and suggest that deregulated CD30 signaling contributes to the neoplastic features of H-RS cells.
Nonaka
Mizuho
M
Department of Molecular Virology, Graduate School of Medicine, Tokyo Medical and Dental University, 1-5-45 Bunkyo-ku, Tokyo 113-8510, Japan.
Horie
Ryouichi
R
Itoh
Kinji
K
Watanabe
Toshiki
T
Yamamoto
Naoki
N
Yamaoka
Shoji
S
D000818:Animals; D002455:Cell Division; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic; D005434:Flow Cytometry; D017930:Genes, Reporter; D006689:Hodgkin Disease / Q000473:pathology / Q000503:physiopathology*; D006801:Humans; D017730:Ki-1 Antigen / Q000235:genetics / Q000502:physiology*; D051381:Rats; D016539:Reed-Sternberg Cells / Q000473:pathology / Q000502:physiology*; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection; D014407:Tumor Cells, Cultured
D017730:Ki-1 Antigen