Regulation of estrogen receptor and epidermal growth factor receptor by tamoxifen under high and low estrogen environments in MCF-7 cells grown in athymic mice

The purpose of this study was to investigate whether tamoxifen (TAM) treatm ent causes a downregulation of estrogen receptor (ER) and whether TAM induc es epidermal growth factor receptor-1 (EGFR). We investigated the expressio n of ER and EGFR after the treatment of TAM in MCF-7 tumors grown in athymi c mice under high and low estrogen environments. MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release 17 beta-estr adiol (E-2) pellet. The E-2 pellets were removed after 3 weeks of E-2 treat ment. Animals were then divided into the following 4 groups: i) an E-2 (0.7 2 mg/pellet) pellet [E-2((+))]; ii) an E-2 and a TAM (5 mg/pellet) pellets [E-2((+))TAM]; iii) no treatment [E-2((-))]; iv) a TAM pellet [E-2((-))TAM] . A significant reduction in tumor size was observed in the estrogen-deplet ed group [E-2((-)) and E-2((-))TAM] compared with the estrogen-completed gr oup [E-2((+)) and E-2((+))TAM]. TAM inhibited estrogen-stimulated growth in the estrogen-completed mice. No additional reduction of the tumor by TAM w as observed in the estrogen-depleted mice. Both ER and EGFR protein levels in the tumors of the estrogen-depleted mice were higher than in the estroge n-completed mice. Expression of ER and EGFR protein was increased by TAM in the estrogen-completed mice, however it was decreased by TAM in the estrog en-depleted mice. Changes of ER and EGFR protein levels were similar in all treatments. Transforming growth factor-alpha (TGF-alpha) in tumors, which is known as a ligand of EGFR and as an estrogen-inducible protein in ER pos itive MCF-7 cells, was decreased by TAM in the estrogen-completed mice, by contrast, it was increased by TAM in the estrogen-depleted mice. Downregula tion of ER was observed in TAM-treated mice in an estrogen-depleted environ ment, this action of TAM was similar to E-2. These results suggest that inc rease of EGFR expression does not lead to a loss of ER after short-term TAM treatment in MCF-7 tumors.