The biologic role for nuclear factor-kappaB in disease and its potential involvement in mucosal injury associated with anti-neoplastic therapy.
Oral mucosal barrier injury (mucositis) is a frequent, painful, serious, dose-limiting toxicity associated with many anti-neoplastic drugs and radiation to the head and neck. Results of recent studies suggest that mucositis is the result of a complex series of interactive biological events that take place in the submucosa and epithelium. The nuclear transcription factor NF-kappaB has been implicated in the control of a broad range of biological responses, the activation of a large number of specific cellular genes, and the determination of the fate of cells exposed to ionizing radiation and anti-neoplastic drugs. Of particular importance to mucositis is the fact that NF-kappaB regulates key elements in the apparent sequence that leads to normal tissue toxicity. Not the least of these is the effect that NF-kappaB activation has on apoptosis. In particular, a paradox exists between the potential pro-apoptotic effect NF-kappaB exerts on normal cells, and the anti-apoptotic and cytoprotective effect it causes in tumor cells. This paper provides a review of the structure and function of NF-kappaB and speculates how its apparent enigmatic effect on normal and tumor cells may occur.
Sonis
Stephen T
ST
Department of Oral Medicine and Diagnostic Sciences, Harvard School of Dental Medicine, Boston, MA 02115, USA. Ssonis@partners.org
D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D016371:Cranial Irradiation / Q000009:adverse effects; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009061:Mouth Mucosa / Q000187:drug effects / Q000528:radiation effects; D016328:NF-kappa B / Q000187:drug effects / Q000502:physiology*; D015533:Transcriptional Activation
D000970:Antineoplastic Agents; D016328:NF-kappa B