Estrogen-Dependent Rapid Activation of Protein Kinase C in Estrogen Receptor-Positive MCF-7 Breast Cancer Cells and Estrogen Receptor-Negative HCC38 Cells Is Membrane-Mediated and Inhibited by Tamoxifen

We examined protein kinase C (PKC) in the regulation of breast cancer cells by estrogen. Estrogen receptor (ER)- positive (+) MCF-7 and ER-negative (−) HCC38 cells were treated with 17β-estradiol (E2) or E2-BSA, which cannot enter the cell. E2 and E2-BSA rapidly increased PKC-α in both cells via phosphatidylinositol-dependent phospholipase C and G protein, but not phospholipase A2 or arachidonic acid. In MCF-7 cells, E2 and E2-BSA had comparable effects, maximal at 90 min. In HCC38 cells, PKC was maximal at 9 min, with E2-BSA more than E2. Tamoxifen blocked estrogen-dependent PKC in MCF-7 cells and reduced it in HCC38 cells. ER-antagonist ICI 182780, ER-agonist diethylstilbestrol, and antibodies to ERα and ERβ had no effect. E2 stimulated [3H]thymidine incorporation in MCF-7 only; E2-BSA had no effect. Tamoxifen did not alter E2-dependent increases in MCF-7 cells, whereas ICI 182780 reduced DNA synthesis in control and E2-treated cultures. PKC activity was positively correlated with tumor severity in 133 ...