title: NF-kappaB1 (p50) homodimers contribute to transcription of the bcl-2 oncogene.
abstract: The bcl-2 proto-oncogene is frequently expressed in human cancer. Although bcl-2 was first cloned as the t(14;18) translocation breakpoint from human follicular B-cell lymphoma, it has become apparent that many cell types express bcl-2 because of transcriptional regulation. As such, several transcription factors have been demonstrated to activate expression of bcl-2, including NF-kappaB. We investigated the role of NF-kappaB1 (p50) homodimers in the expression of Bcl-2 in two murine B-cell lymphoma cell lines: LY-as, an apoptosis-proficient line with low Bcl-2 protein expression and no nuclear NF-kappaB activity, and LY-ar, a nonapoptotic line with constitutive p50 homodimer activity and 30 times more Bcl-2 protein expression than LY-as. We found that nuclear p50 homodimer activity correlated with Bcl-2 expression in these cell types and identified several sites within the bcl-2 5'-flanking region that p50 was capable of binding. In vitro transcription revealed that recombinant p50 enhanced the production of run-off transcripts from the bcl-2 P1 promoter. Additional in vitro transcription experiments suggested the sites by which p50 afforded this effect. We conclude that the p50 homodimer is capable of transcriptional activation of the bcl-2 gene and suggest that its nuclear activity contributes to the expression of bcl-2 in LY-ar cells.
authors.affiliation: Department of Experimental Radiation Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
authors.forename: J F
authors.initials: JF
authors.lastname: Kurland
authors.forename: R
authors.initials: R
authors.lastname: Kodym
authors.forename: M D
authors.initials: MD
authors.lastname: Story
authors.forename: K B
authors.initials: KB
authors.lastname: Spurgers
authors.forename: T J
authors.initials: TJ
authors.lastname: McDonnell
authors.forename: R E
authors.initials: RE
authors.lastname: Meyn
mesh_terms: D000818:Animals; D017209:Apoptosis; D001665:Binding Sites; D015153:Blotting, Western; D002154:Calpain / Q000494:pharmacology; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D019281:Dimerization; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051379:Mice; D016328:NF-kappa B / Q000737:chemistry* / Q000378:metabolism*; D052002:NF-kappa B p50 Subunit; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; C000715470:MAS1 protein, human; D016328:NF-kappa B; D052002:NF-kappa B p50 Subunit; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D002154:Calpain