Both estradiol and tamoxifen decrease proliferation and invasiveness of cancer cells transfected with a mutated estrogen receptor

• Published in: The Journal of steroid biochemistry and molecular biology 1997-04, Vol.61 (1), p.11-17
• Main Authors: Garcia, Marcel, Derocq, Danielle, Platet, Nadine, Bonnet, Sandrine, Brouillet, Jean-Paul, Touitou, Isabelle, Rochefort, Henri
• Format: Article
• Language: English
• Subjects: Animals; Biological and medical sciences; Cell Division - drug effects; Estradiol - analogs & derivatives; Estradiol - pharmacology; Estrogen Antagonists - pharmacology; Gynecology. Andrology. Obstetrics; Mammary gland diseases; Medical sciences; Mice; Mice, Inbred BALB C; Mice, Nude; Mutation; Neoplasm Invasiveness; Neoplasms, Experimental - genetics; Neoplasms, Experimental - pathology; Polyunsaturated Alkamides; Rats; Receptors, Estrogen - genetics; Tamoxifen - analogs & derivatives; Tamoxifen - pharmacology; Transfection; Tumors
• ISSN: 0960-0760; 1879-1220
• DOI: 10.1016/S0960-0760(96)00255-5

Previous studies have shown that, after wild-type estrogen receptor (ER) transfection in ER-negative breast cancer cells, estradiol but not tamoxifen prevents growth, invasiveness and metastasis of these cells in mice. Because an ER mutation at position 400 converts the triphenylethylene antiestrogen, OH-tamoxifen into a full estrogen agonist, we transfected this mutated form of human ER in an ER-negative rat cancer cell line. This was aimed at inducing an inhibitory, estrogen-like response of tamoxifen in these cells. In two stable ER-positive transfectants, OH-tamoxifen inhibited cell growth and invasiveness in vitro as efficiently as estradiol. The pure antiestrogen, ICI 164,384, was not agonistic alone and antagonized estrogen action. In contrast, the three compounds were ineffective in control mock-transfected cells. When injected into ovariectomized nude mice, ER-negative mock-transfected cells formed tumours which were significantly stimulated by estradiol and inhibited by tamoxifen treatment. This indicates that estradiol and taxmoxifen altered the growth of ER-negative tumours via a general effect on the host response. Surprisingly, the hormone responsiveness of ER-positive tumours developed from ER-transfected cells did not significantly differ from that of ER-negative (mock-transfected) tumours. We conclude that transfection of a mutated human estrogen receptor inhibited, through an estrogenic activity of tamoxifen, the growth and invasiveness of these cancer cells in vitro. However, the low expression of ER did not allowed us to obtain the same effect of tamoxifen in vivo.