The role of metalloproteinases and their inhibitors in regulating mammary epithelial morphology and function in vivo


An intact basement membrane (BM) is essential for the proper function, differentiation and morphology of many epithelial cells. The disruption or loss of this BM occurs during normal development as well as in the disease state. To examine the importance of the BM during mammary gland development in vivo, we generated transgenic mice which inappropriately express autoactivating isoforms of the matrix metalloproteinase, stromelysin-1. The mammary glands from these mice are both functionally and morphologically altered throughout development. The mammary glands from virgin transgenic mice had supernumerary branches and showed precocious development of alveoli that expressed β-casein. During midpregnancy, the alveolar structures were collapsed and mouse mammary epithelial cells underwent apoptosis. We have now documented a dramatic incidence of breast tumors in several independent lines of these mice. These data suggest that overexpression of SL-1 and disruption of the BM may play a key role in mammary gland branching morphogenesis, apoptosis and breast cancer induction and progression.

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Correspondence to Zena Werb.

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Sympson, C.J., Talhouk, R.S., Bissell, M.J. et al. The role of metalloproteinases and their inhibitors in regulating mammary epithelial morphology and function in vivo. Perspectives in Drug Discovery and Design 2, 401–411 (1995).

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Key words

  • ECM
  • Proteinases
  • Mammary gland
  • Apoptosis
  • Breast cancer