Details

Autor(en) / Beteiligte

• NONAKA, Mizuho
• HORIE, Ryouichi
• ITOH, Kinji
• WATANABE, Toshiki
• YAMAMOTO, Naoki
• YAMAOKA, Shoji

Titel

Aberrant NF-κB2/p52 expression in Hodgkin/Reed-Sternberg cells and CD30-transformed rat fibroblasts

Ist Teil von

• Oncogene, 2005-06, Vol.24 (24), p.3976-3986

Ort / Verlag

Basingstoke: Nature Publishing

Erscheinungsjahr

2005

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• Overexpression of CD30 and constitutive nuclear factor-κB (NF-κB) 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-κB activity, which is comprised of the p50 and RelA subunits. We report here enhanced expression of NF-κB2/p52 and RelB-containing NF-κB 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-κB (IκB) 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 IκB kinase activation, proteasome-dependent p100 processing, and NF-κB-dependent cell transformation. Our results thus indicate that CD30 triggers the noncanonical NF-κB activation pathway, and suggest that deregulated CD30 signaling contributes to the neoplastic features of H-RS cells.