NF-kappa B inhibits apoptosis in murine mammary epithelia

Clarkson, Richard W. E. ORCID: https://orcid.org/0000-0001-7389-8673, Heeley, JoannaLL., Chapman, Rachel, Aillet, Fabienne, Hay, Ronald T., Wyllie, Andrew and Watson, Christine J. 2000. NF-kappa B inhibits apoptosis in murine mammary epithelia. Journal of Biological Chemistry 275 (17) , pp. 12737-12742. 10.1074/jbc.275.17.12737

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Abstract

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.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Biosciences European Cancer Stem Cell Research Institute (ECSCRI)
Publisher:	American Society for Biochemistry and Molecular Biology
ISSN:	0021-9258
Last Modified:	22 Jun 2023 10:01
URI:	https://orca.cardiff.ac.uk/id/eprint/63323

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