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
|
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: | Schools > Biosciences Research Institutes & Centres > 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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