NF-kappa B inhibits apoptosis in murine mammary epithelia

The transcription factor NF-kappa B is a key modulator of apoptosis in a va riety of cell types, but to date this specific function of NF-kappa B has n ot been demonstrated in epithelia, Here, we describe the activation of NF-k appa B during post-lactational involution of the mouse mammary gland, a per iod of extensive apoptosis of luminal epithelial cells. Significantly, acti ve NF-kappa B localized exclusively to nonapoptotic epithelial cells both i n vivo and in the mammary epithelial cell line, KIM-2, transduced with an N F-kappa B-dependent green fluorescent protein reporter, Activation of NF-ka ppa B in vitro coincided with a decrease in the cytosolic repressor, I kapp a B alpha. Furthermore, induction of NF-kappa B either by extracellular lig ands or, more specifically, by inhibition of the I kappa B repressor with a denoviral constructs expressing antisense mRNA, resulted in enhanced surviv al of KIM-2 cells. Therefore, although coincident with induction of apoptos is both in vivo and in vitro, NF-kappa B appeared to exert a selective surv ival function in epithelial cells. This study highlights for the first time a role for NF-kappa B in modulating apoptosis in epithelium.