Tamoxifen activates phospholipase D in human MCF-7 breast cancer cells : Involvement of protein kinase C

초록

The activation of phospholipase D (PLD) in MCF-7 human breast cancer cells treated with tamoxifen has been investigated. Tamoxifen treatment resulted in a both dose- and time-dependent increases in PLD activity. There was a nearly maximum saturated rise in PLD activity at the dose of 10μM tamoxifen showing a 3.3-fold increase within 3 h. Also we observed increased mRNA levels and protein levels of PLD upto 48h in tamoxifen-treated MCF-7 cells. When the cells were pretreated for 24 h with phorbol myristate acetate (PMA) to down-regulate protein kinase C (PKC), PLD stimulation by tamoxifen was largely abolished. These studies indicate that in MCF-7 cells, tamoxifen can induce increased PLD expression resulting increased PLD activity, and that PKC activation is involved in this stimulation.