The nuclear factor κB subunits RelA/p65 and c-Rel potentiate but are not required for Ras-induced cellular transformation

Julie L. Hanson, Noel A. Hawke, David Kashatus, Albert S. Baldwin

Research output: Contribution to journalArticle

44 Citations (Scopus)

Abstract

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 κB (NF-κB). Supportive of the importance of NF-κB in transformation, Ras-induced cellular transformation can be suppressed by expression of IκBα, an inhibitor of NF-κB, or by dominant-negative forms of the upstream activator IκB kinase (IKK). However, conclusive evidence for a requirement for NF-κB subunits in oncogenic transformation has not been reported. Furthermore, there is little understanding of the gene targets controlled by NF-κB 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-κB 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-κB for their expression and that likely play contributory roles in promoting Ras-induced oncogenic transformation.

Original languageEnglish (US)
Pages (from-to)7248-7255
Number of pages8
JournalCancer Research
Volume64
Issue number20
DOIs
StatePublished - Oct 15 2004

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Transcription Factors
ras Genes
Oncogene Proteins
Microarray Analysis
Transcriptional Activation
Signal Transduction
Phosphotransferases
Fibroblasts
Genes

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The nuclear factor κB subunits RelA/p65 and c-Rel potentiate but are not required for Ras-induced cellular transformation. / Hanson, Julie L.; Hawke, Noel A.; Kashatus, David; Baldwin, Albert S.

In: Cancer Research, Vol. 64, No. 20, 15.10.2004, p. 7248-7255.

Research output: Contribution to journalArticle

Hanson, Julie L. ; Hawke, Noel A. ; Kashatus, David ; Baldwin, Albert S. / The nuclear factor κB subunits RelA/p65 and c-Rel potentiate but are not required for Ras-induced cellular transformation. In: Cancer Research. 2004 ; Vol. 64, No. 20. pp. 7248-7255.
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