CD30 activates both the canonical and alternative NF-κB pathways in anaplastic large cell lymphoma cells

Casey W. Wright, Julie M. Rumble, Colin S. Duckett

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63 Scopus citations


CD30 is a member of the tumor necrosis factor receptor superfamily whose expression is up-regulated on anaplastic large cell lymphoma (ALCL) and Hodgkin lymphoma (HL) cells. Many different outcomes of CD30 stimulation have been reported, including cell cycle arrest, apoptosis, and activation of the prosurvival transcription factor, NF-κB, although this last activity ismuchless well defined in ALCL cells. In order to better understand the signaling properties of CD30 in cancer, we established a system for the stimulation of CD30 with its physiological ligand. Using this system, CD30 was stimulated on ALCL and HL cells, and the subsequent CD30 signaling properties were characterized. We show that a fraction of ALCL cells rapidly underwent apoptosis following CD30 stimulation, whereas HL cells were unaffected. The surviving ALCL cells exhibited robust activation of both the canonical and alternative NF-κB pathways as measured by nuclear translocation of RelA, p50, RelB, and p52, and this culminated in the transactivation of classical NF-κB-responsive genes. With prolonged CD30 stimulation, ALCL cells underwent cell cycle arrest that correlated with expression of the cell cycle inhibitor p21waf1. Furthermore, p21waf1 expression and cell cycle arrest were found to depend predominantly on the canonical NF-κB pathway, since it was reversed by RNA interference-mediated suppression of RelA. In contrast, suppression of the p100/p52 NF-κB subunit had little effect on p21waf1. These data reveal that in ALCL cells, in contrast to other cell types, CD30 stimulation elicits p21 waf1-mediated arrest through the canonical but not the alternative NF-κB pathway.

Original languageEnglish (US)
Pages (from-to)10252-10262
Number of pages11
JournalJournal of Biological Chemistry
Issue number14
StatePublished - Apr 6 2007
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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