The nuclear factor kappaB subunits RelA/p65 and c-Rel potentiate but are not required for Ras-induced cellular transformation.
Extensive data indicate that oncoproteins, such as oncogenic H-Ras, initiate signal transduction cascades that ultimately lead to the activation of specific transcription factors. We and others have previously demonstrated that Ras activates the inherent transcriptional activation function of the transcription factor nuclear factor kappaB (NF-kappaB). Supportive of the importance of NF-kappaB in transformation, Ras-induced cellular transformation can be suppressed by expression of IkappaBalpha, an inhibitor of NF-kappaB, or by dominant-negative forms of the upstream activator IkappaB kinase (IKK). However, conclusive evidence for a requirement for NF-kappaB subunits in oncogenic transformation has not been reported. Furthermore, there is little understanding of the gene targets controlled by NF-kappaB that might support oncogenic conversion. The data presented here demonstrate that, although both p65 and c-Rel enhance the frequency of Ras-induced cellular transformation, these NF-kappaB subunits are not essential for Ras to transform spontaneously immortalized murine fibroblasts. Microarray analysis identified a set of genes induced by Ras that is dependent on NF-kappaB for their expression and that likely play contributory roles in promoting Ras-induced oncogenic transformation.
Hanson
Julie L
JL
Lineberger Comprehensive Cancer Center, Curriculum in Genetics and Molecular Biology, and Department of Biology, University of North Carolina, Chapel Hill, North Carolina, USA.
Hawke
Noel A
NA
Kashatus
David
D
Baldwin
Albert S
AS
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D004622:Embryo, Mammalian / Q000166:cytology; D005347:Fibroblasts / Q000502:physiology; D011905:Genes, ras / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D016328:NF-kappa B / Q000502:physiology*; D020569:Proto-Oncogene Proteins c-rel / Q000502:physiology*; D051996:Transcription Factor RelA; D018631:ras Proteins / Q000502:physiology*
D016328:NF-kappa B; D020569:Proto-Oncogene Proteins c-rel; D051996:Transcription Factor RelA; D018631:ras Proteins