The Role of Matrilysin, a Matrix Metalloproteinase, in Mammary Tumorigenesis.

The goal of this project is to test the hypothesis that the expression of matrilysin in mammary epithelial cells plays a causal role in the progression and metastasis of mammary carcinomas using a transgenic mouse model system. We have successfully generated transgenic mice expressing the metalloproteinase matrilysin, under the control of the mammary specific MMTV promoter/enhancer. In this report we demonstrate that matrilysin accelerates the development of mammary tumors in the MMTV-neu transgenic animals. Current studies involve investigating the possibility that matrilysin is proteolytically processing members of the EGF/erbB signal transduction pathway, thereby constitutively activating this pathway and accelerating mammary tumor formation.