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 responsible for malignant progression. In the present study, we investigated the potent inhibitory effects of an antiestrogen, toremifene, on PKC-mediated cellular adhesion. A phorbol ester, phorbol 12-myristate 13-acetate (PMA), significantly enhanced alpha2beta1 integrin-dependent adhesion 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 demonstrated that the PMA-induced alpha2beta1-dependent cellular adhesion was accompanied with elevated expression of alpha2beta1+integrin subunit on the cell surface. However, toremifene did not affect the elevated expression levels of these integrins but rather the avidity of alpha2beta1 integrin. We concluded that toremifene inhibited cellular adhesion activated by PMA, probably through mechanism which inhibits PKC.
Maemura
M
M
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan.
Iino
Y
Y
Horiguchi
J
J
Takei
H
H
Horii
Y
Y
Koibuchi
Y
Y
Yokoe
T
T
Takeyoshi
I
I
Ohwada
S
S
Morishita
Y
Y
D001943:Breast Neoplasms / Q000201:enzymology / Q000473:pathology*; D002273:Carcinogens; D002277:Carcinoma / Q000201:enzymology / Q000473:pathology*; D002448:Cell Adhesion / Q000187:drug effects*; D004794:Enzyme Repression; D004965:Estrogen Antagonists / Q000494:pharmacology*; D006801:Humans; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D017312:Toremifene / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D002273:Carcinogens; D004965:Estrogen Antagonists; D017312:Toremifene; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate