| First Author | Vargo-Gogola T | Year | 2002 |
| Journal | Cancer Res | Volume | 62 |
| Issue | 19 | Pages | 5559-63 |
| PubMed ID | 12359768 | Mgi Jnum | J:79688 |
| Mgi Id | MGI:2388782 | Citation | Vargo-Gogola T, et al. (2002) Matrilysin (Matrix Metalloproteinase-7) Selects for Apoptosis-resistant Mammary Cells in Vivo. Cancer Res 62(19):5559-63 |
| abstractText | 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. |
