Aberrant NF- B2 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 comp...
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Veröffentlicht in: | Oncogene 2005-06, Vol.24 (24), p.3976-3986 |
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Zusammenfassung: | 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. |
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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/sj.onc.1208564 |