Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo.

Vargo-Gogola T, Fingleton B, Crawford HC, Matrisian LM
Cancer Res. 2002 62 (19): 5559-63

PMID: 12359768

Overexpression of the matrix metalloproteinase matrilysin (matrix metalloproteinase-7) in the mouse mammary gland promotes mammary hyperplasia and accelerates the onset of oncogene-induced mammary tumors. In cell culture models, acute exposure of cells coexpressing Fas and Fas ligand (FasL) to matrilysin induces apoptosis, whereas chronic exposure to matrilysin selects for apoptosis-resistant cells. We now demonstrate that matrilysin promotes resistance to apoptosis in vivo. Matrilysin expression increased apoptosis in the involuting mammary gland of mice that had undergone a single pregnancy and lactation cycle. Premature basement membrane disruption was detected in matrilysin-expressing mice, which could account for the increase in apoptosis. However, multiparous mice, in which the involuting mammary epithelial cells have been repeatedly exposed to matrilysin, show a significant decrease in apoptosis. Mammary tissue from multiparous matrilysin-expressing mice showed decreased FasL expression, suggesting that loss of FasL is at least one mechanism of matrilysin-induced resistance to apoptosis. We propose that matrilysin promotes mammary tumor formation by enhancing the selection of cells that are resistant to apoptosis.

MeSH Terms (11)

Animals Apoptosis Female Hyperplasia Lactation Mammary Glands, Animal Mammary Tumor Virus, Mouse Matrix Metalloproteinase 7 Mice Mice, Transgenic Pregnancy

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