NF-kappaB activates Bcl-2 expression in t(14;18) lymphoma cells

Oncogene. 2002 May 30;21(24):3898-908. doi: 10.1038/sj.onc.1205483.


The t(14;18) translocation, which is characteristic of follicular lymphoma, results in the overexpression of the bcl-2 gene dependent upon regulatory elements within the bcl-2 5' flanking region and the immunoglobulin heavy chain gene enhancers. Conflicting evidence exists on the effects of NF-kappaB expression on Bcl-2 levels in different cell types. Lymphoma cells with the t(14;18) translocation show high levels of nuclear NF-kappaB proteins. We observed decreased levels of endogenous Bcl-2 when the IkappaBalpha-super-repressor was expressed in a t(14;18) cell line. Deletion analysis of the bcl-2 promoter indicated that the repressive effect of the IkappaBalpha-super-repressor occurred through a region that contained no NF-kappaB consensus sequences. This highly active region contained a c-AMP response element (CRE) and several Sp1 binding sites. Chromatin immunoprecipitation assays with antibodies specific for the NF-kappaB and CREB/ATF family members, as well as Sp1, resulted in the isolation of this IkappaBalpha-super-repressor responsive region of the bcl-2 promoter. Mutation of the CRE and the two Sp1 sites in different combinations in bcl-2 reporter constructs resulted in the loss of bcl-2 promoter repression by the IkappaBalpha-super-repressor. We therefore conclude that the activation of bcl-2 by NF-kappaB in t(14;18) lymphoma cells is mediated through the CRE and Sp1 binding sites.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Apoptosis
  • Binding Sites
  • Blotting, Western
  • Cell Line
  • Chromatin / metabolism
  • Chromosomes, Human, Pair 14*
  • Chromosomes, Human, Pair 18*
  • Cyclic AMP / metabolism
  • Dose-Response Relationship, Drug
  • Electrophoresis, Polyacrylamide Gel
  • Genetic Vectors
  • Humans
  • Immunoblotting
  • Luciferases / metabolism
  • Lymphoma / metabolism*
  • Models, Genetic
  • Mutation
  • NF-kappa B / metabolism*
  • Plasmids / metabolism
  • Precipitin Tests
  • Promoter Regions, Genetic
  • Protein Binding
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sp1 Transcription Factor / metabolism
  • Transfection
  • Translocation, Genetic*
  • Tumor Cells, Cultured
  • Tumor Necrosis Factor-alpha / metabolism
  • Ultraviolet Rays


  • Chromatin
  • NF-kappa B
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Messenger
  • Sp1 Transcription Factor
  • Tumor Necrosis Factor-alpha
  • Cyclic AMP
  • Luciferases