Rochefort H
Biochimie. 1982 Feb;64(2):89-98. doi: 10.1016/s0300-9084(82)80411-2.
Synthetic antiestrogens such as Tamoxifen (Nolvadex) are currently used to treat postmenopausal breast cancer. Their mechanism of action is reviewed at the cellular and molecular level, through data of the literature and the current view of the author. Synthetic antiestrogens are mostly acting directly on breast cancer cells by interacting with the estrogen receptor (RE). They prevent estrogen action by competing with estrogens on the cytosol RE. The resulting complex is partially activated resulting in its nuclear localisation and a partial and dissociated stimulation of the expression of estrogen responsive genes. The explanation of the antitumoral effect of these drugs is more controversial, since the regulation of cell proliferation is not only due to estrogens but also to other hormones and factors. The antiestrogens can therefore block cancer cell growth by inhibiting estrogen action, or by a RE medicated cytotoxic effect and/or by any other mechanism involving indirect effects, or binding to other proteins than the RE.
诸如他莫昔芬（诺瓦得士）之类的合成抗雌激素药物目前用于治疗绝经后乳腺癌。通过文献数据及作者的当前观点，在细胞和分子水平对其作用机制进行综述。合成抗雌激素大多通过与雌激素受体（RE）相互作用直接作用于乳腺癌细胞。它们通过在胞质溶胶RE上与雌激素竞争来阻止雌激素作用。形成的复合物被部分激活，导致其定位于细胞核，并对雌激素反应性基因的表达产生部分且解离的刺激。这些药物抗肿瘤作用的解释更具争议性，因为细胞增殖的调节不仅归因于雌激素，还归因于其他激素和因子。因此，抗雌激素可以通过抑制雌激素作用、或通过RE介导的细胞毒性作用和/或通过涉及间接作用的任何其他机制、或通过与RE以外的其他蛋白质结合来阻断癌细胞生长。
