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 carcinoma and could potentially prevent the development of mammary cancer. While it is widely clinically used, its exact mechanisms of action are not yet fully elucidated. MCF-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-desmethyltamoxifen, restore the function of E-cadherin in MCF-7/6 cells. In an aggregation assay, 10(-6) M tamoxifen significantly increases the aggregation of MCF-7/6 cells. This effect is abrogated by a monoclonal antibody against E-cadherin (HECD-1), is fast (within 30 min), and does not require de novo protein synthesis. Tamoxifen was also found to inhibit the invasion of MCF-7/6 cells in organ culture. Our data is the first demonstration that tamoxifen can activate the function of an invasion suppressor molecule and suggest that the restoration of E-cadherin function may contribute to the therapeutic benefit of tamoxifen in breast cancer patients.
Bracke
M E
ME
Laboratory of Experimental Cancerology, University Hospital, Gent, Belgium.
Charlier
C
C
Bruyneel
E A
EA
Labit
C
C
Mareel
M M
MM
Castronovo
V
V
D001943:Breast Neoplasms / Q000473:pathology*; D015820:Cadherins / Q000187:drug effects*; D002118:Calcium / Q000502:physiology; D002448:Cell Adhesion / Q000187:drug effects; D005260:Female; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D013629:Tamoxifen / Q000031:analogs & derivatives / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D015820:Cadherins; D013629:Tamoxifen; C016601:afimoxifene; D007334:Insulin-Like Growth Factor I; C028787:N-desmethyltamoxifen; D002118:Calcium