NF-kappaB inhibits apoptosis in murine mammary epithelia.
The transcription factor NF-kappaB is a key modulator of apoptosis in a variety of cell types, but to date this specific function of NF-kappaB has not been demonstrated in epithelia. Here, we describe the activation of NF-kappaB during post-lactational involution of the mouse mammary gland, a period of extensive apoptosis of luminal epithelial cells. Significantly, active NF-kappaB localized exclusively to nonapoptotic epithelial cells both in vivo and in the mammary epithelial cell line, KIM-2, transduced with an NF-kappaB-dependent green fluorescent protein reporter. Activation of NF-kappaB in vitro coincided with a decrease in the cytosolic repressor, IkappaBalpha. Furthermore, induction of NF-kappaB either by extracellular ligands or, more specifically, by inhibition of the IkappaB 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-kappaB appeared to exert a selective survival function in epithelial cells. This study highlights for the first time a role for NF-kappaB in modulating apoptosis in epithelium.
Clarkson
R W
RW
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, United Kingdom. rwec2@mole.bio.cam.ac.uk
Heeley
J L
JL
Chapman
R
R
Aillet
F
F
Hay
R T
RT
Wyllie
A
A
Watson
C J
CJ
D000256:Adenoviridae / Q000378:metabolism; D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D002460:Cell Line; D016373:DNA, Antisense / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004848:Epithelium / Q000378:metabolism / Q000473:pathology; D005260:Female; D017930:Genes, Reporter; D020672:I-kappa B Proteins / Q000378:metabolism; D007150:Immunohistochemistry; D008024:Ligands; D008321:Mammary Glands, Animal / Q000378:metabolism / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000096:biosynthesis / Q000502:physiology*; D011247:Pregnancy; D013997:Time Factors; D051996:Transcription Factor RelA
D017304:Annexin A5; D016373:DNA, Antisense; D020672:I-kappa B Proteins; D008024:Ligands; D016328:NF-kappa B; D051996:Transcription Factor RelA