Heterogeneity of Binding Sites for Triphenylethylene Antiestrogens in Estrogen Target Tissues
Most of the interest in understanding the mechanism of action of triphenylethylene antiestrogens (Fig. 1) arises from their ability to induce weak estrogenic effects, to antagonize many of the actions of estrogens and to induce the remission of human breast cancer particularly during the post-menopausal period (Legha et al., 1978). In particular, these compounds are able to suppress estrogen-induced uterine growth (Jordan et al., 1977) and to antagonize estrogen-induced growth of human breast cancer cells which contain estrogen receptor (Lippman et al., 1976). In this regard, triphenylethylene antiestrogens are used for understanding the mechanism by which estrogens regulate cell growth. However, triphenylethylene antiestrogens are also able to inhibit the growth of estrogen sensitive and estrogen receptor containing human breast cancer cells, even in the absence of estrogens (Lippman et al., 1976). The attempt to understand the mechanism of action of both estrogen and antiestrogens awaits the elucidation of the molecular events and interactions which occur at the subcellular and cellular level. In recent years, multiple interactions of triphenylethylene antiestrogens have been reported at the subcellular level: a) the interaction with the estrogen receptor system (Terenius, 1971; Lippman et al., 1976; Horwitz and McGuire, 1978), and b) the binding of these compounds to specific binding sites distinct from the estrogen receptor in several experimental models such as the chick oviduct (Sutherland and Foo, 1979), rat uterus (Faye et al., 1980), fetal guinea pig uterus (Gulino and Pasqualini, 1980), human mammary cancer (Sutherland and Murphy, 1980) and human myometrium (Kon, 1983). The aim of this paper is to summarize the data so far known about the interactions of triphenylethylene antiestrogens with target cells at the subcellular level.
KeywordsHuman Breast Cancer Cell Ratio Competitor Fetal Organ Estrogen Receptor Level Antiestrogen Binding Site
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- Coezy, E., Borgna, J. L., and Rochefort, H., 1982, Tamoxifen and metabolites in MCF-7 cells: correlation between binding to estrogen receptors and inhibition of cell growth, Cancer Res., 42: 317.Google Scholar
- Green, M. D., Whybourne, A. M., Taylor, I. W., and Sutherland, R. L., 1981, Effects of antioestrogens on the growth and cell kinetics of cultured human mammary carcinoma cells, in: “Non-Steroidal Antioestrogens,” R. L. Sutherland, and V. C. Jordan, eds, Academic Press, Sidney.Google Scholar
- Pasqualini, J. R., and Nguyen, B. L., 1976, Mise en évidence des récepteurs cytosoliques et nucléaires de l’oestradiol dans l’utérus de foetus de cobaye, C.R. Acad. Sci., ( Série D) (Paris ) 283: 413.Google Scholar
- Pasqualini, J. R., Sumida, C., Gulino, A., Nguyen, B. L., Tardy, J., and Gelly, C., 1980, Recent data on receptors and biological action of estrogens and antiestrogens in the fetal uterus of guinea pig, in: “Hormones and Cancer,” S. Iacobelli, R. J. B. King, H. R. Lindner, and M. E. Lippman, eds, Raven Press, New York.Google Scholar
- Sumida, C., and Pasqualini, J. R., 1980, Dynamic studies on estrogen responses in fetal guinea pig uterus: effect of estradiol administration on estradiol receptor, progesterone receptor and uterine growth, J. Receptor Res., 1: 439.Google Scholar
- Terenius, L., 1971, Structure-activity relationships of antiestrogens with regard to interaction with 1713-estradiol in the mouse uterus and vagina, Acta Endocrinol. ( Copenh. ), 66: 431.Google Scholar
- Terpstra, A. H. M., Woodward, C. J. H., and Sanchez-Muniz F. J., 1981, Improved techniques for the separation of serum lipoproteins by density gradient ultracentrifugation: visualization by prestaining and rapid separation of serum lipoproteins from small volumes of serum, Anal. Biochem., 111: 149.PubMedCrossRefGoogle Scholar