NF-kB inhibits apoptosis in murine mammary epithelia

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