NF-κB inhibits apoptosis in murine mammary epithelia

被引:103
作者
Clarkson, RWE
Heeley, JL
Chapman, R
Aillet, F
Hay, RT
Wyllie, A
Watson, CJ
机构
[1] Univ Cambridge, Dept Pathol, Cambridge CB2 1QP, England
[2] Univ St Andrews, Sch Biol, St Andrews KY16 9ST, Fife, Scotland
[3] Western Gen Hosp, Mol Med Ctr, Sir Alistair Currie Canc Res Campaign Labs, Edinburgh EH4 2XU, Midlothian, Scotland
关键词
D O I
10.1074/jbc.275.17.12737
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:12737 / 12742
页数:6
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