Abstract
TGF beta 1 treatment of B cell lymphomas decreases c-myc gene expression and induces apoptosis. Since we have demonstrated NF-kappa/Rel factors play a key role in transcriptional control of c-myc, we explored the effects of TGF beta1 on WEHI 231 immature B cells. A reduction in NF-kappa B/Rel activity followed TGF beta 1 treatment. In WEHI 231 and CH33 cells, we observed an increase in I kappa B alpha, a specific NF-kappa B/Rel inhibitor, due to transcriptional induction. Engagement of surface CD40 or ectopic c-Rel led to maintenance of NF-kappa B/Rel and c-Myc expression and protection of WEHI 231 cells from TGF beta 1-mediated apoptosis. Ectopic c-Myc expression overrode apoptosis induced by TGF beta 1. Thus, downmodulation of NF-kappa B/Rel reduces c-Myc expression, which leads to apoptosis in these immature B cell models of clonal deletion. The inhibition of NF-kappa B/Rel activity represents a novel TGF beta signaling mechanism.
Publication types
-
Research Support, Non-U.S. Gov't
-
Research Support, U.S. Gov't, P.H.S.
MeSH terms
-
Animals
-
Apoptosis / drug effects*
-
B-Lymphocytes / drug effects*
-
B-Lymphocytes / metabolism
-
CD40 Ligand
-
Down-Regulation / drug effects
-
Down-Regulation / genetics
-
Genes, myc / immunology
-
Ligands
-
Membrane Glycoproteins / pharmacology
-
Mice
-
NF-kappa B / antagonists & inhibitors*
-
NF-kappa B / biosynthesis
-
Proto-Oncogene Proteins / antagonists & inhibitors*
-
Proto-Oncogene Proteins / biosynthesis
-
Proto-Oncogene Proteins / genetics*
-
Proto-Oncogene Proteins c-rel
-
RNA, Messenger / biosynthesis
-
Transcription Factor RelB
-
Transcription Factors*
-
Transcription, Genetic / immunology*
-
Transforming Growth Factor beta / pharmacology*
-
Tumor Cells, Cultured
Substances
-
Ligands
-
Membrane Glycoproteins
-
NF-kappa B
-
Proto-Oncogene Proteins
-
Proto-Oncogene Proteins c-rel
-
RNA, Messenger
-
Relb protein, mouse
-
Transcription Factors
-
Transforming Growth Factor beta
-
CD40 Ligand
-
Transcription Factor RelB