Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix.
Apoptosis (programmed cell death) plays a major role in development and tissue regeneration. Basement membrane extracellular matrix (ECM), but not fibronectin or collagen, was shown to suppress apoptosis of mammary epithelial cells in tissue culture and in vivo. Apoptosis was induced by antibodies to beta 1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1 beta converting enzyme (ICE) correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These results suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression.
Boudreau
N
N
Life Sciences Division, Lawrence Berkeley Laboratory, Berkeley, CA 94720.
Sympson
C J
CJ
Werb
Z
Z
Bissell
M J
MJ
D000818:Animals; D017209:Apoptosis; D001485:Basement Membrane; D020170:Caspase 1; D002460:Cell Line; D003094:Collagen; D003546:Cysteine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D005109:Extracellular Matrix / Q000378:metabolism / Q000502:physiology*; D005353:Fibronectins; D015971:Gene Expression Regulation, Enzymologic; D019012:Integrin beta1; D016023:Integrins / Q000276:immunology; D008321:Mammary Glands, Animal / Q000166:cytology* / Q000201:enzymology; D019278:Matrix Metalloproteinase 3; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D015853:Cysteine Proteinase Inhibitors; D005353:Fibronectins; D019012:Integrin beta1; D016023:Integrins; D012333:RNA, Messenger; D003094:Collagen; D003546:Cysteine Endopeptidases; D020170:Caspase 1; D008666:Metalloendopeptidases; D019278:Matrix Metalloproteinase 3