The study investigates the role of extracellular matrix (ECM) in suppressing apoptosis in mammary epithelial cells. The authors found that basement membrane ECM, but not fibronectin or collagen, prevents apoptosis in both tissue culture and in vivo. Apoptosis was induced by antibodies to β1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1β converting enzyme (ICE), a known inducer of apoptosis, correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These findings suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression. The study also demonstrates that proteolytic degradation of ECM during mammary gland involution leads to the loss of the differentiated state, induction of ICE expression, and ultimately apoptotic cell death.The study investigates the role of extracellular matrix (ECM) in suppressing apoptosis in mammary epithelial cells. The authors found that basement membrane ECM, but not fibronectin or collagen, prevents apoptosis in both tissue culture and in vivo. Apoptosis was induced by antibodies to β1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1β converting enzyme (ICE), a known inducer of apoptosis, correlated with the loss of ECM, and inhibitors of ICE activity prevented apoptosis. These findings suggest that ECM regulates apoptosis in mammary epithelial cells through an integrin-dependent negative regulation of ICE expression. The study also demonstrates that proteolytic degradation of ECM during mammary gland involution leads to the loss of the differentiated state, induction of ICE expression, and ultimately apoptotic cell death.