Trends in Cell Biology
NF-κB: tumor promoter or suppressor?
Section snippets
NF-κB is a tumor promoter
The suggestion that the members of NF-κB family might behave as tumorigenic transcription factors was first put forward upon the cloning of the p50–p105 (NF-κB1) subunit 15, 16. Analysis of the NF-κB1 sequence immediately revealed homology to v-rel, a potent transforming oncogene of the avian reticuloendotheliosis virus [17], and its cellular counterpart the protooncogene c-rel. Further support for a role of NF-κB subunits in cancer came with the discovery of the gene encoding p52–p100 (NF-κB2)
Is NF-κB a tumor suppressor?
DNA damage, oncogene activation and cellular stress are well-established activators of the p53 tumor suppressor; however, they also induce DNA-binding and transcriptional activity of NF-κB [2]. Activation of p53 can result in either cell-cycle arrest or induction of apoptosis, whereas as discussed above, the induction of NF-κB is generally associated with resistance to apoptosis and proliferation. This suggested that mechanisms must exist within the cell to integrate the activities of these two
A revised model for the role of NF-κB in cancer
An important implication of the hypothesis that NF-κB can function as a tumor suppressor is that its behavior in normal untransformed cells might be quite different from that in transformed and malignant tumor cells. Oncogenic stimulation of untransformed cells will not only activate DNA-binding and transcriptional activity of NF-κB but will also activate the tumor suppressor programs of the cell (Figure 2) 12, 13, 21. These tumor suppressors, in particular p53 and ARF, can then act to inhibit
Acknowledgements
N.D.P. is the recipient of a Royal Society University Research Fellowship. Many thanks to Sonia Rocha and Kirsteen Campbell for their critical reading of this manuscript and helpful suggestions.
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