TAMOXIFEN RESTORES THE E-CADHERIN FUNCTION IN HUMAN BREAST-CANCER MCF-7 6 CELLS AND SUPPRESSES THEIR INVASIVE PHENOTYPE/

Tamoxifen is an antiestrogen used in adjuvant therapy of breast carcin oma and could potentially prevent the development of mammary cancer. W hile it is widely clinically used, its exact mechanisms of action are not yet fully elucidated. MCP-7/6 cells are estrogen receptor-positive invasive human breast cancer cells with a functionally inactive cell surface E-cadherin. In this study, we report that tamoxifen, and to a lesser extent its metabolites 4-OH-tamoxifen and N-desmethyl-tamoxifen , restore the function of E-cadherin in MCF-7/6 cells. In an aggregati on assay, 10(-6) M tamoxifen significantly increases the aggregation o f MCF-7/6 cells. This effect is abrogated by a monoclonal antibody aga inst E-cadherin (HECD-1), is fast (within 30 min), and does not requir e de novo protein synthesis. Tamoxifen was also found to inhibit the i nvasion of MCP-7/6 cells in organ culture. Our data is the first demon stration that tamoxifen can activate the function of an invasion suppr essor molecule and suggest that the restoration of E-cadherin function may contribute to the therapeutic benefit of tamoxifen in breast canc er patients.