The NF-κB/IκB signaling system:: A molecular target in breast cancer therapy

The nuclear factor kappaB (NFkappaB) superfamily of eukaryotic transcription factors plays an important role in carcinogenesis. NF-kappaB and its regulators are linked to various signal transduction pathways as well as transcriptional activation events that mediate critical stages of cell proliferation. These intracellular signaling processes are thought to regulate chromatin structure to accommodate transcription, apoptosis, cellcycle control, and cell transformation. In this capacity, uncontrolled or aberrant NF-kappaB activity may, in part, be responsible for breast cancer progression. Constitutive NF-kappaB expression may predict the metastatic potential of breast tumors, indicating early use of adjuvant therapy and suggesting NF-kappaB inhibition as a novel treatment. In this review, we discuss the regulatory mechanisms and physiological significance of NF-kappaB activation, and highlight recent advances in the development of NF-kappaB as an integral mediator of mammary carcinogenesis. (C) 2004 Elsevier Inc. All rights reserved.