Cell-cell contact down-regulates expression of membrane type metalloproteinase-1 (MT1-MMP) in a mouse mammary gland...

Membrane type matrix metalloproteinase (MT-MMP), which possesses a C-terminal transmembrane domain, is expressed on the cell membrane (Sato et al., 1994, Nature 370: 61-65). It was suspected, therefore, that the expression of MT-MMPs might be regulated by cell-cell interactions. We examined the patterns of MT1-MMP expression in a mouse mammary gland epithelial cell line, HC11, which is capable of responding to prolactin in vitro. HC11 cells form well-differentiated monolayer of cuboidal epithelium at confluence. During the log growth phase, cells which are well dispersed and seemingly migrating actively, or located at the periphery of small colonies, reacted strongly with an anti-MT1-MMP antibody, whereas no MT1-MMP immunoreactivity was detected in the cells which established cell-cell contact with adjacent cells. At confluence, the HC11 cells lost MT1-MMP immunoreactivity completely. Northern blot analysis revealed that MT1-MMP mRNA is present at a high level in HC11 cells during the log phase of growth. Although MT1-MMP immunoreactivity disappeared by the 1st day confluence was reached, the decline of MT1-MMP mRNA levels started only a few days later. The discrepancy in the timing of decrease of MT1-MMP protein and that of the transcripts suggests the presence of translational control mechanisms for MT1-MMP expression during cell-cell interaction.