Chalbos D, Galtier F, Emiliani S, Rochefort H
Institut National de la Santé et de la Recherche Médicale U 148, Unit-Hormones and Cancer, Montpellier, France.
J Biol Chem. 1991 May 5;266(13):8220-4.
Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its gene transcription and mRNA stabilization (Joyeux, C., Rochefort, H., and Chalbos, D. (1989) Mol. Endocrinol. 4, 681-686). In vitro run-on transcription assays show that RU486, in contrast to progestin, inhibits FAS transcription by 40-50%. Moreover and surprisingly, anti-progestin RU486 also stabilizes FAS mRNA 3- to 4-fold in MCF7 cells as measured by chase experiments in the presence of actinomycin D or cordycepin or after short cell labeling with [3H]uridine. Dexamethasone is inefficient in increasing the half-life of FAS mRNA in MCF7 cells. RU486 had no effect on MDA-MB 231 cells which contain glucocorticoid but no progesterone receptors, indicating that the progesterone receptor is implicated in this regulation. RU486-induced mRNA stabilization allows delayed accumulation of FAS mRNA. These results indicate that the progesterone receptor can be activated separately to stimulate gene transcription or stabilize mRNA.
孕激素可诱导乳腺癌细胞系中的脂肪酸合成酶（FAS），既能增加其基因转录，又能使信使核糖核酸（mRNA）稳定（乔尤克斯，C.，罗什福尔，H.，以及沙尔博斯，D.（1989年）《分子内分泌学》4卷，681 - 686页）。体外连续转录分析表明，与孕激素相反，米非司酮可使FAS转录抑制40% - 50%。此外，令人惊讶的是，通过在放线菌素D或放线菌酮存在下的追踪实验，或在用[³H]尿苷进行短时间细胞标记后测量发现，抗孕激素米非司酮在MCF7细胞中也能使FAS mRNA稳定3至4倍。地塞米松在增加MCF7细胞中FAS mRNA半衰期方面效率不高。米非司酮对含有糖皮质激素受体但无孕激素受体的MDA - MB 231细胞没有影响，这表明孕激素受体参与了这种调节。米非司酮诱导的mRNA稳定使得FAS mRNA延迟积累。这些结果表明，孕激素受体可被分别激活以刺激基因转录或稳定mRNA。
