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

Tracy Vargo-Gogola, Barbara Fingleton, Howard C. Crawford, Lynn M. Matrisian

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)5559-5563
Number of pages5
JournalCancer Research
Volume62
Issue number19
StatePublished - Oct 1 2002
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Vargo-Gogola, T., Fingleton, B., Crawford, H. C., & Matrisian, L. M. (2002). Matrilysin (matrix metalloproteinase-7) selects for apoptosis-resistant mammary cells in vivo. Cancer Research, 62(19), 5559-5563.