The transcription factor nuclear factor-kappa B and cancer

Since the discovery of nuclear factor-kappa B (NF-kappa B) in 1986, many studies have been conducted showing the link between the NF-kappa B signalling pathway and control of the inflammatory response. Today it is well known that control of the inflammatory response and apoptosis is closely related to the activation of NF-kappa B. Three NF-kappa B activation pathways exist. The first (the classical pathway) is normally triggered in response to microbial and viral infections or exposure to pro-inflammatory cytokines that activate the tripartite IKK complex, leading to phosphoryiation-induced I kappa B degradation and depends mainly on IKK beta activity. The second (the alternative pathway), leads to selective activation of p52:RelB dimers by inducing the processing of the NF-kappa B2/p100 precursor protein, which mostly occurs as a heterodimer with RelB in the cytoplasm. This pathway is triggered by certain members of the tumour necrosis factor cytokine family, through selective activation of IKK alpha homodimers by the upstream kinase NIK. The third pathway is named CK2 and is IKK independent. NF-kappa B acts through the transcription of anti-apoptotic proteins, leading to increased proliferation of cells and tumour growth. It is also known that some drugs act directly in the inhibition of NF-kappa B, thus producing regulation of apoptosis; some examples are aspirin and corticosteroids. Here we review the role of NF-kappa B in the control of apoptosis, its link to oncogenesis, the evidence of several studies that show that NF-kappa B activation is closely related to different cancers, and finally the potential target of NF-kappa B as cancer therapy.