NF-κB Inhibits Apoptosis in Murine Mammary Epithelia*

The transcription factor NF-κB is a key modulator of apoptosis in a variety of cell types, but to date this specific function of NF-κB has not been demonstrated in epithelia. Here, we describe the activation of NF-κB during post-lactational involution of the mouse mammary gland, a period of extensive apoptosis of luminal epithelial cells. Significantly, active NF-κB localized exclusively to nonapoptotic epithelial cells both in vivoand in the mammary epithelial cell line, KIM-2, transduced with an NF-κB-dependent green fluorescent protein reporter. Activation of NF-κB in vitro coincided with a decrease in the cytosolic repressor, IκBα. Furthermore, induction of NF-κB either by extracellular ligands or, more specifically, by inhibition of the IκB repressor with adenoviral constructs expressing antisense mRNA, resulted in enhanced survival of KIM-2 cells. Therefore, although coincident with induction of apoptosis both in vivo and in vitro, NF-κB appeared to exert a selective survival function in epithelial cells. This study highlights for the first time a role for NF-κB in modulating apoptosis in epithelium.