| MAGI-1, a scaffolding protein present at adherens and tight junctions, interacts with a multitude of signaling molecules including PTEN, a bona fide tumor suppressor; beta-catenin, a pivotal signaling molecule; and RPTP beta, a receptor tyrosine phosphatase. Previous studies have demonstrated variable expression of MAGI-1 among a panel of human breast cancer cell lines. The ability of MAGI-1 to interact with both tumor suppressor and oncogenic signaling molecule has prompted studies to test the biological consequences of expressing MAGI-1 in breast cancer cell lines. For this, wild-type MAGI-1 as well as PDZ domain binding mutants were stably expressed in MDA-MB-157 cells, which has an almost undetectable level of MAGI-1. Biological assays were performed in order to determine the tumorigenic phenotypes of the transfectants. Cellular proliferation and migration were substantially suppressed by wild type MAGI-1 and those effects were sensitive to the levels of protein being expressed. In addition, the proliferative capacity of the stable cell clones was directly correlated with the levels of free beta-catenin. Furthermore, these suppressor effects of wild-type MAGI-1 appear to be dependent on the presence of an intact PDZ 2 domain. |
