Tetracycline (Tet) -inducible and repressible expression systems have provided important information about the roles of various tumor-associated enzymes in cancer progression. In the 23 July issue of Cell, Sternlicht et al. used a Tet - regulated expression system of the metalloproteinase (MMP) stromelysin-1 (Str-1) to investigate its role in carcinoma development. MMPs typically promote tumor cell invasion by disrupting extracellular matrix barriers, but are also believed to affect cell signaling. The authors observed that in the presence of Tet, when Str1 expression is repressed, mammary epithelial cells grow as a sheet, expressing the protein cytokeratin (upper panel–red stain). These cells develop into normal duct and gland-like structures when injected into mice. Removal of Tet (lower panel) induces Str1 expression, causing an epithelial to mesenchymal transition characterized by downregulation of cytokeratins and upregulation of the mesenchymal cell marker vimentin (green stain). Str1 expression therefore converts normal mammary epithelial cells into highly infiltrative mesenchymal tumor cells both in vitro and in vivo. Sternlicht and colleagues think that MMPs such as Str1 promote this differentiation by activating the E-cadherin/β-catenin signaling pathway involved in both normal development and abnormal neoplastic progression.