Berry M, Metzger D, Chambon P
Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
EMBO J. 1990 Sep;9(9):2811-8. doi: 10.1002/j.1460-2075.1990.tb07469.x.
Various oestrogen responsive reporter genes and vectors expressing truncated or chimeric human oestrogen receptors (hER) containing either of the two independent hER transcriptional activation functions (TAF-1 and TAF-2) have been transfected into HeLa cells, chicken embryo fibroblast (CEF) or yeast cells to investigate the agonistic activity of the anti-oestrogen 4-hydroxytamoxifen (OHT). We demonstrate that the agonistic effect of OHT on the whole hER is due to the cell-type and promoter-context dependent activity of TAF-1. In similar experiments, we show that the anti-oestrogen, ICI 164,384, does not exhibit any oestrogenic activity and, therefore, acts always as a pure antagonist, even though it does not inhibit the activity of the isolated TAF-1. We also confirm that the wild type human oestrogen receptor has no ligand independent transcriptional activity. The implications of our results for the variable antagonist/agonist activity of anti-oestrogens in vivo are discussed.
已将各种雌激素反应性报告基因以及表达截短或嵌合型人雌激素受体（hER）的载体转染至HeLa细胞、鸡胚成纤维细胞（CEF）或酵母细胞中，这些受体含有两种独立的hER转录激活功能（TAF-1和TAF-2）之一，以研究抗雌激素4-羟基他莫昔芬（OHT）的激动活性。我们证明，OHT对完整hER的激动作用归因于TAF-1的细胞类型和启动子背景依赖性活性。在类似实验中，我们表明抗雌激素ICI 164,384不表现出任何雌激素活性，因此始终作为纯拮抗剂起作用，即使它不抑制分离的TAF-1的活性。我们还证实野生型人雌激素受体没有配体非依赖性转录活性。讨论了我们的结果对体内抗雌激素可变拮抗剂/激动剂活性的影响。
