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J Biol Chem, Vol. 275, Issue 17, 12737-12742, April 28, 2000
From the The transcription factor NF-
NF-
B Inhibits Apoptosis in Murine Mammary Epithelia*
§,,
,,, and
Department of Pathology, University of
Cambridge, Tennis Court Road, Cambridge CB2 1QP, the School
of Biology, Biomedical Science Building, University of St. Andrews, St.
Andrews, Fife KY16 9ST, and ¶ Sir Alistair Currie Cancer
Research Campaign Laboratories, Molecular Medicine Centre, Western
General Hospital, Crewe Road, Edinburgh EH4 2XU, Midlothian, United
Kingdom
B is a key
modulator of apoptosis in a variety of cell types, but to date this
specific function of NF-B has not been demonstrated in epithelia.
Here, we describe the activation of NF-B during post-lactational
involution of the mouse mammary gland, a period of extensive apoptosis
of luminal epithelial cells. Significantly, active NF-B localized
exclusively to nonapoptotic epithelial cells both in vivo
and in the mammary epithelial cell line, KIM-2, transduced with an
NF-B-dependent green fluorescent protein reporter.
Activation of NF-B in vitro coincided with a decrease in
the cytosolic repressor, IB
. Furthermore, induction of NF-B
either by extracellular ligands or, more specifically, by inhibition of
the IB 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-B appeared to exert a
selective survival function in epithelial cells. This study highlights
for the first time a role for NF-B in modulating apoptosis in epithelium.
*
This work was funded by the Home Office (UK) and grants from
the Melville Trust and the Cancer Research Campaign.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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