ALTERATIONS IN BETA-CATENIN PHOSPHORYLATION AND PLAKOGLOBIN EXPRESSION IN HUMAN BREAST-CANCER CELLS

Because the cell adhesion molecule epithelial cadherin (E-cadherin) is absent in many invasive carcinomas, we transfected the E-cadherin gen e into E-cadherin-negative, invasive breast cancer cell lines BT549 an d HS578t to investigate the role of E-cadherin in invasive behavior. A lthough the transfected E-cadherin could mediate calcium-dependent agg regation to E-cadherin-transfected L-cells, morphology and invasivenes s of the breast cancer cells were not altered. We investigated the str ength of the linkage of the transfected E-cadherin to the actin cytosk eleton by examining the Triton X-100 solubility of the transfected E c adherin. In BT549 and HS578t cells, a large proportion of the transfec ted E-cadherin was Triton soluble, whereas in E-cadherin-positive MCF- 7 cells, Triton-insoluble E-cadherin was apparent at cell-cell borders . Interaction of E-cadherin with the actin cytoskeleton is thought to be mediated by the E-cadherin-binding proteins alpha-catenin, beta-cat enin, and plakoglobin. We found normal levels of alpha-catenin and bet a-catenin in BT549 and HS578t cells; however, low levels of plakoglobi n were expressed in these cells compared to those found in weakly inva sive MCF-7 cells. Furthermore, levels of tyrosine phosphorylation of b eta-catenin were elevated in E-cadherin-transfected BT549 and HS578t c ells compared to MCF-7 cells. We conclude that other factors such as t he expression and appropriate posttranslational modification of cadher in-associated proteins must be in place for E-cadherin to be fully fun ctional, i.e., to alter invasiveness. During cancer progression, loss of E-cadherin expression itself or multiple other mechanisms that lead to loss of cell-cell adhesion (mutation, loss of catenin expression, alterations in phosphorylation) may contribute to a more metastatic ph enotype.