title: Nfkb 1 is dispensable for Myc-induced lymphomagenesis.
abstract: Rel/NF-kappaB transcription factors are critical arbiters of immune responses, cell survival, and transformation, and are frequently deregulated in cancer. The p50 NF-kappaB 1 component of Rel/NF-kappaB DNA-binding dimers regulates genes involved in both cell cycle traverse and apoptosis. Nfkb 1 loss accelerates B cell growth and leads to increased B cell turnover in vivo, phenotypes akin to those manifested in B cells of Emu-Myc transgenic mice, a model of human Burkitt lymphoma. Interestingly, Emu-Myc B cells express reduced levels of cytoplasmic and nuclear NF-kappaB 1 and have reduced Rel/NF-kappaB DNA-binding activity, suggesting that Myc-mediated repression of NF-kappaB 1 might mediate its proliferative and apoptotic effects on B cells. Furthermore, Nfkb 1 expression was reduced in the majority of Emu-Myc lymphomas and was also suppressed in human Burkitt lymphoma. Nonetheless, loss of Nfkb 1 did not appreciably affect Myc's proliferative or apoptotic responses in B cells and had no effect on lymphoma development in Emu-Myc mice. Therefore, Nfkb 1 is dispensable for Myc-induced lymphomagenesis..
authors.affiliation: Department of Biochemistry, St Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105, USA.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Keller
authors.forename: Jonas A
authors.initials: JA
authors.lastname: Nilsson
authors.forename: Kirsteen H
authors.initials: KH
authors.lastname: Maclean
authors.forename: Jennifer B
authors.initials: JB
authors.lastname: Old
authors.forename: John L
authors.initials: JL
authors.lastname: Cleveland
mesh_terms: D000818:Animals; D001483:Base Sequence; D002051:Burkitt Lymphoma / Q000235:genetics; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D052002:NF-kappa B p50 Subunit / Q000235:genetics / Q000502:physiology*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000502:physiology*
chemical_list: D017931:DNA Primers; D052002:NF-kappa B p50 Subunit; C489548:NFKB1 protein, human; D016271:Proto-Oncogene Proteins c-myc; D004247:DNA