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Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells

Item Type:Article
Title:Constitutive NF-kappaB maintains high expression of a characteristic gene network, including CD40, CD86, and a set of antiapoptotic genes in Hodgkin/Reed-Sternberg cells
Creators Name:Hinz, M. and Loeser, P. and Mathas, S. and Krappmann, D. and Doerken, B. and Scheidereit, C.
Abstract:Constitutively activated nuclear factor (NF)-κB is observed in a variety of neoplastic diseases and is a hallmark of the malignant Hodgkin and Reed-Sternberg cells (H/RS) in Hodgkin lymphoma. Given the distinctive role of constitutive NF-κB for H/RS cell viability, NF-κB-dependent target genes were searched for by using adenoviral expression of the super-repressor IκBΔN. A surprisingly small but characteristic set of genes, including the cell-cycle regulatory protein cyclin D2, the antiapoptotic proteins Bfl-1/A1, c-IAP2, TRAF1, and Bcl-X L, and the cell surface receptors CD86 and CD40 were identified. Thus, constitutive NF-κB activity maintains expression of a network of genes, which are known for frequent, marker-like expression in primary or cultured H/RS cells. Intriguingly, CD40, which is able to activate CD86 or Bcl-X L via NF-κB, is itself transcriptionally regulated by NF-κB through a promoter proximal binding site. NF-κB inhibition resuited in massive spontaneous and p53-independent apoptosis, which could be rescued by ectopic expression of Bcl-X L, underscoring its dominant role in survival of H/RS cells. Hence, NF-κB controls a signaling network in H/RS cells, which promotes tumor cell growth and confers resistance to apoptosis.
Source:Blood
ISSN:0006-4971
Publisher:American Society of Hematology (U.S.A.)
Volume:97
Number:9
Page Range:2798-2807
Date:1 January 2001
Official Publication:https://doi.org/10.1182/blood.V97.9.2798
PubMed:View item in PubMed

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