INHIBITORY EFFECTS OF AN ANTIESTROGEN, TOREMIFENE ON THE PHORBOL ESTER-INDUCED ADHESIVE CAPACITY OF BREAST-CARCINOMA CELLS

Previous studies have revealed that protein kinase C (PKC) is responsi ble for malignant progression. In the present study, we investigated t he potent inhibitory effects of an antiestrogen, toremifene, on PKC-me diated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-ace tate (PMA), significantly enhanced alpha 2 beta 1 integrin-dependent a dhesion of MCF-7 breast carcinoma cells. This PMA-induced adhesion was partially inhibited by incubating cells with toremifene prior to PMA exposure in a time- and dose-dependent manner. FACS analysis demonstra ted that the PMA-induced alpha 2 beta 1-dependent cellular adhesion wa s accompanied with elevated expression of alpha 2 and beta 1 integrin subunit on the cell surface. However, toremifene did not affect the el evated expression levels of these integrins but rather the avidity of alpha 2 beta 1 integrin. We concluded that toremifene inhibited cellul ar adhesion activated by PMA, probably through mechanism which inhibit s PKC.