p53 and NF-κB are two key effectors in the chemotherapy-induced genotoxic response. Although p53 is a universal inducer of apoptotosis in many stress responses, including the genotoxic response, the role of nuclear factor (NF)-κB is not consistent and was reported to both counteract and mediate apoptosis. Although the reason for the apparent contradictory effects of NF-κB is not understood, it may partly be related to the reported cross-regulation of NF-κB and p53. Thus far, all studies exploring the cross-talk between p53 and NF-κB in conjunction with apoptosis have been performed in tissue-cultured cells and may therefore not faithfully represent conditions that prevail within a chemotherapy-subjected organism. To address this concern, we examined the respective roles of NF-κB and p53 in a liver model of doxorubicin-induced DNA damage. Using this animal model, we report that NF-κB is activated in response to doxorubicin-induced genotoxic stress and exerts a pronounced protective effect in opposing chemotherapy-induced tissue damage. Importantly, the activation of NF-κB occurs independently of p53 status. Furthermore, although p53 is also induced in this in vivo system, its induction is independent of NF-κB and does not contribute to the extent of tissue damage. These findings may have important implications with respect to the potential use of NF-κB modulators in cancer therapy.
|Original language||American English|
|Number of pages||6|
|State||Published - 1 Jan 2003|