Growth Factors and Metalloproteinases in Breast Cancer Development and Progression

摘要

The matrix metalloproteinase matrilysin is expressed in human breast cancers as well as in normal-appear epithelium surrounding benign and malignant breast lesions. We explored the potential role of matrilysin in mammary tumor development using a transgenic mouse approach. Multiparous female mice expressing matrilysin in the mammary glands developed hyperplastic alveolar nodules. Transgenic mice expressing both the oncogene neu and matrilysin in the mammary glands demonstrated a marked acceleration in the time of mammary tumor onset. The tumor promoting effect of matrilysin was not due to a direct effect on an erbB-related signal transduction pathway. Using a somatic cell hybridization approach, we determined that there is a dominant repressor of matrilysin expression in normal mammary epithelium that is apparently lost with malignant transformation. Although we have been unable to molecularly identify this repressor, this approach has the potential of identifying novel tumor suppressors involved in breast cancer.