Suppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix

We examined apoptosis in vivo in transgenic mice expressing the stromelysin-1 gene under control of the whey acidic milk protein promoter, which is activated in mid- to late pregnancy

N. Boudreau

2006

Scholarcy highlights

  • Apoptosis plays a major role in development and tissue regeneration
  • mammary epithelial cells that were attached to culture dishes coated with either fibronectin or type I collagen displayed a degree of apoptosis similar to MECs cultured on plastic, indicating that suppression of apoptosis required an intact basement membrane extracellular matrix
  • We examined apoptosis in vivo in transgenic mice expressing the stromelysin-1 gene under control of the whey acidic milk protein promoter, which is activated in mid- to late pregnancy
  • To determine whether apoptosis of MECs was mediated by interleukin-1β converting enzyme, a known inducer of apoptosis in mammalian cells, we transfected CID-9 cells with a vector encoding crmA, a viral gene product that inhibits the enzymatic activity of ICE
  • To determine whether the regulation of ICE expression was directly related to the presence of ECM, we examined ICE mRNA expression in CID-9 cells
  • BACMK reduced DNA laddering in CID-9 cells by up to 80% after 5 days as compared to uninhibited controls
  • Our data cannot distinguish between ICE and as yet unidentified ICE gene family members that might be blocked by active site-directed inhibitors or recognized by antibodies to ICE, we show that survival requires adhesion, and specialized β1 integrin–mediated signals derived from specific ECM components
  • The proteolytic degradation of extracellular matrix such as occurs during mammary gland involution leads to the loss of the differentiated state, induction of interleukin-1β converting enzyme expression and activity, and apoptotic cell death both in vivo and in culture

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