Growth Factors and Metalloproteinases in Breast Cancer Development and Progression.
Abstract
We show that the metalloproteinase matrilysin dramatically accelerates the development of neu-induced mammary tumors by decreasing the time to tumor onset and increasing the percent of animals developing tumors. In addition, MMTV-matrilysin transgenic mice develop preneoplastic alveolar nodules in multiparous females. We speculated that the mechanism of tumor acceleration was via the induction of an EGF receptor signaling pathway, but an analysis of the interaction and phosphorylation of erbB family members demonstrated no evidence for activation of these pathways. Using human breast cancer cell lines, we demonstrated that the expression of matrilysin in MDA-MB-468 cells requires the presence of an EGF signaling pathway. However, in addition to the positive activation of matrilysin, the loss of a negative repressor of matrilysin expression is also required for constitutive matrilysin expression as demonstrated by fusion with the immortal breast epithelial cell line HBL 100. Determining: (1) the mechanism of matrilysin acceleration of mammary tumorigenesis and (2) characterization of the matrilysin repressor will be pursued in future studies.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 1997
- Accession Number
- ADA336736
Entities
People
- Lynn M. Matrisian
Organizations
- Vanderbilt University