Synthesis of gelatinases by rat mammary epithelial and myoepithelial cell lines.

The synthesis of metalloproteinases capable of degrading the basement membrane is an important factor contributing to the involution of the mammary gland after the young are weaned. To investigate the cellular source of mammary gland metalloproteinases, we have studied the synthesis of gelatinases by rat mammary epithelial and myoepithelial cell lines immortalized with a temperature-sensitive T-antigen. At 39.5 degrees C, the temperature at which the cells display increased differentiated characteristics, myoepithelial cells synthesize 40- to 160-fold greater amounts of three gelatinases (M(r)s-72, 92, and 135 kDa) than epithelial cells. The gelatinases are preferentially secreted through the basolateral surface of myoepithelial cells. Growth of cells in the presence of a variety of growth factors and cytokines demonstrates the differential regulation of the synthesis of the 72- and 92-kDa gelatinases. These results suggest that the myoepithelial cell is a major source of mammary gland metalloproteinases.