The regulatory effect of tamoxifen on fibronectin expression in estrogen-dependent MCF-7 breast carcinoma cells.
We investigated the regulatory effect of tamoxifen (TAM) on fibronectin (FN) expression in estrogen-dependent MCF-7 breast carcinoma cells both in vitro and in vivo. in vitro, MCF-7 cells were cultured with 17beta-estradiol (E2) and/or TAM. In the animal experiment in vivo, MCF-7 tumors were grown in ovariectomized athymic mice by implanting a sustained release E2 pellet. The E2 pellets were removed after 3 weeks of E2 treatment. Animals were then divided into four groups: 1) an E2 (0.72 mg/pellet) pellet [E2(+)]; 2) an E2 and a TAM (5 mg/pellet) pellet [E2(+)TAM]; 3) no treatment [E2(-)] and 4) a TAM pellet [E2(-)TAM]. Following each treatment for 4 weeks, all animals were sacrificed and tumors were removed. Specimens, cells (in vitro) or tumors (in vivo), were homogenized and assayed for FN by Western blots. In the in vitro experiment, FN expression in MCF-7 cells decreased by incubating with 10(-9) M E2 and increased with 10(-6) M TAM. The effect of TAM increasing FN expression was inhibited by incubation accompanied with 10(-9) M E2 or 1 microg/ml transforming growth factor-beta (TGF-beta) neutralizing antibody. In the in vivo animal experiment FN expression in the tumors of E2(+) mice was lower than that of E2(-) mice. However, TAM increased FN expression in the tumors regardless of E2 pellet. These results suggest that TAM increases FN expression of MCF-7 breast carcinoma cells and that these regulatory effects of TAM on FN expression are partly mediated by TAM-induced TGF-beta.
Horii
Yoshio
Y
Department of Thoracic and Visceral Organ Surgery, Gunma University Graduate School of Medicine, Maebashi, Gunma 371-8511, Japan. y.horii@jcom.home.ne.jp
Takei
Hiroyuki
H
Koibuchi
Yukio
Y
Horiguchi
Jun
J
Maemura
Michio
M
Iino
Yuichi
Y
Morishita
Yasuo
Y
D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015153:Blotting, Western; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005353:Fibronectins / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy* / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology*; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000637:transplantation
D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D005353:Fibronectins; D016212:Transforming Growth Factor beta; D013629:Tamoxifen