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) treatment causes a downregulation of estrogen receptor (ER) and whether TAM induces epidermal growth factor receptor-1 (EGFR). We investigated the expression of ER and EGFR after the treatment of TAM in MCF-7 tumors grown in athymic mice under high and low estrogen environments. MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release 17beta-estradiol (E2) pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into the following 4 groups: i) an E2 (0. 72 mg/pellet) pellet [E2(+)]; ii) an E2 and a TAM (5 mg/pellet) pellets [E2(+)TAM]; iii) no treatment [E2(-)]; iv) a TAM pellet [E2(-)TAM]. A significant reduction in tumor size was observed in the estrogen-depleted group [E2(-) and E2(-)TAM] compared with the estrogen-completed group [E2(+) and E2(+)TAM]. TAM inhibited estrogen-stimulated growth in the estrogen-completed mice. No additional reduction of the tumor by TAM was 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 estrogen-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 estrogen-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 positive MCF-7 cells, was decreased by TAM in the estrogen-completed mice, by contrast, it was increased by TAM in the estrogen-depleted mice. Downregulation of ER was observed in TAM-treated mice in an estrogen-depleted environment, this action of TAM was similar to E2. These results suggest that increase of EGFR expression does not lead to a loss of ER after short-term TAM treatment in MCF-7 tumors.
Koibuchi
Y
Y
Second Department of Surgery, Gunma University School of Medicine, Maebashi, Gunma 371-8511, Japan.
Iino
Y
Y
Uchida
T
T
Andoh
T
T
Horii
Y
Y
Nagasawa
M
M
Horiguchi
J
J
Maemura
M
M
Takei
H
H
Yokoe
T
T
Morishita
Y
Y
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000627:therapeutic use*; D066246:ErbB Receptors / Q000032:analysis*; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000737:chemistry / Q000188:drug therapy*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D011960:Receptors, Estrogen / Q000032:analysis*; D013629:Tamoxifen / Q000627:therapeutic use*; D016211:Transforming Growth Factor alpha / Q000032:analysis; D014183:Transplantation, Heterologous
D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D016211:Transforming Growth Factor alpha; D013629:Tamoxifen; D004958:Estradiol; D066246:ErbB Receptors