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

The nuclear factor κB (NFκB) superfamily of eukaryotic transcription factors plays an important role in carcinogenesis. NF-κB 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, cell-cycle control, and cell transformation. In this capacity, uncontrolled or aberrant NF-κB activity may, in part, be responsible for breast cancer progression. Constitutive NF-κB expression may predict the metastatic potential of breast tumors, indicating early use of adjuvant therapy and suggesting NF-κB inhibition as a novel treatment. In this review, we discuss the regulatory mechanisms and physiological significance of NF-κB activation, and highlight recent advances in the development of NF-κB as an integral mediator of mammary carcinogenesis.