Suppression of ICE and Apoptosis in Mammary Epithelial Cells by Extracellular Matrix

TLDR

Apoptosis is essential for development and tissue regeneration. Basement membrane ECM suppresses apoptosis of mammary epithelial cells by integrin‑dependent inhibition of ICE, whereas loss of ECM or β1 integrin blockade induces ICE expression and apoptosis.

Abstract

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 β 1 integrins or by overexpression of stromelysin-1, which degrades ECM. Expression of interleukin-1β 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.