NF- kappa B2/p100 induces Bcl-2 expression.
The NF-kappaB2/p100 and bcl-3 genes are involved in chromosomal translocations described in chronic lymphocytic leukemias (CLL) and non-Hodgkin's lymphomas, and nuclear factor kappaB (NF-kappaB) protects cancer cells against apoptosis. Therefore, we investigated whether this transcription factor could modulate the expression of the Bcl-2 antiapoptotic protein. Bcl-2 promoter analysis showed multiple putative NF-kappaB binding sites. Transfection assays of bcl-2 promoter constructs in HCT116 cells showed that NF-kappaB can indeed transactivate bcl-2. We identified a kappaB site located at position -180 that can only be bound and transactivated by p50 or p52 homodimers. As p50 and p52 homodimers are devoid of any transactivating domains, we showed that they can transactivate the bcl-2 promoter through association with Bcl-3. We also observed that stable overexpression of p100 and its processed product p52 can induce endogenous Bcl-2 expression in MCF7AZ breast cancer cells. Finally, we demonstrated that, in breast cancer and leukemic cells (CLL), high NF-kappaB2/p100 expression was associated with high Bcl-2 expression. Our data suggest that Bcl-2 could be an in vivo target gene for NF-kappaB2/p100.
Viatour
P
P
Center for Cellular and Molecular Therapy, University of Liège, Liège, Belgium.
Bentires-Alj
M
M
Chariot
A
A
Deregowski
V
V
de Leval
L
L
Merville
M-P
MP
Bours
V
V
D000081242:B-Cell Lymphoma 3 Protein; D001402:B-Lymphocytes / Q000473:pathology; D001943:Breast Neoplasms / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000473:pathology; D008297:Male; D016328:NF-kappa B / Q000378:metabolism / Q000502:physiology*; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D011401:Promoter Regions, Genetic; D011518:Proto-Oncogene Proteins / Q000378:metabolism / Q000502:physiology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000235:genetics*; D014157:Transcription Factors; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured
D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D052003:NF-kappa B p52 Subunit; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors