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J Cell Biol. 1996 Dec;135(6 Pt 1):1669-77.

Rescue of mammary epithelial cell apoptosis and entactin degradation by a tissue inhibitor of metalloproteinases-1 transgene.

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  • 1Department of Anatomy, University of California, San Francisco 94143-0750, USA.

Abstract

We have used transgenic mice overexpressing the human tissue inhibitor of metalloproteinases (TIMP)-1 gene under the control of the ubiquitous beta-actin promoter/enhancer to evaluate matrix metalloproteinase (MMP) function in vivo in mammary gland growth and development. By crossing the TIMP-1 transgenic animals with mice expressing an autoactivating stromelysin-1 transgene targeted to mammary epithelial cells, we obtained a range of mice with genetically engineered proteolytic levels. The alveolar epithelial cells of mice expressing autoactivating stromelysin-1 underwent unscheduled apoptosis during late pregnancy. When stromelysin-1 transgenic mice were crossed with mice overexpressing TIMP-1, apoptosis was extinguished. Entactin (nidogen) was a specific target for stromelysin-1 in the extracellular matrix. The enhanced cleavage of basement membrane entactin to above-normal levels was directly related to the apoptosis of overlying mammary epithelial cells and paralleled the extracellular MMP activity. These results provide direct evidence for cleavage of an extracellular matrix molecule by an MMP in vivo.

PMID:
8978831
[PubMed - indexed for MEDLINE]
PMCID:
PMC2133964
Free PMC Article
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