Effect of estradiol and raloxifene on MUC1 expression and adhesive properties of Ishikawa cells

Abstract

The MUC1 is a transmembrane protein with a large mucin-like extracellular domain protruding high above the cell surface. Steroid regulation of MUC1 gene expression is essential, since overexpression of MUC1 may influence the metastatic potential of cancer cells. Our earlier results demonstrated that tamoxifen, alone and combined with estradiol, inhibits MUC1 biosynthesis in endometrial adenocarcinoma cells, in contrast to estradiol. In the present study, we examine the effect of administering raloxifene or estradiol at concentrations of 1 x 10(-8)-5 x 10(-7) M, and both drugs together, on the expression of MUC1 protein, its incorporation into the cell membrane, shedding to culture medium and adhesive properties of cancer cells to the extracellular matrix (ECM). The obtained results demonstrate that raloxifene, to a lesser degree than estradiol, stimulates [3)H]Thr incorporation to the cellular, as well as the extracellular MUC1 protein. Raloxifene-treated cells show a higher cell adhesion to collagen than estradiol-treated cells, especially at lower concentrations of these drugs, probably the result of smaller amounts of sialic acid residues in the terminal glycan chains with T and Tn antigens. Sole administration of raloxifene has a lesser effect on the expression of alpha(2)beta(1) integrin than estradiol, which is in contrast to the combined action of estradiol and raloxifene. Therefore, raloxifene, which stimulates MUC1 expression in cancer cells and inhibits their adhesion to collagen to a lesser degree than estradiol, may be a clinically safe treatment for the endometrium.