Graham J D, Roman S D, McGowan E, Sutherland R L, Clarke C L
Department of Medical Oncology, University of Sydney, Westmead Hospital, New South Wales, Australia.
J Biol Chem. 1995 Dec 22;270(51):30693-700. doi: 10.1074/jbc.270.51.30693.
Human progesterone receptor (PR) expression is controlled by two promoter regions giving rise to transcripts encoding PR A and B proteins. It is unknown whether estrogen and progesterone, the major physiological modulators of PR expression, exert their effects equally on the PR promoters. The aim of this study was to analyze estrogen and progestin effects on PR promoters, PR-encoding transcripts, and PR A and B proteins in T-47D human breast cancer cells. The progestin ORG 2058 caused a prolonged decrease in transcription of the PR gene and also abrogated estrogen stimulation of PR transcription. Estradiol (E2) treatment increased the activity of the B but not the A promoter transfected into T-47D cells. ORG 2058 had no effect on the basal or E2-stimulated activity of either promoter. E2 caused a preferential increase in transcripts derived from promoter B, whereas progestins decreased the levels of all PR transcripts. E2 preferentially increased the concentration of the PR B protein and caused a decrease in the PR A/B ratio. This demonstration that estrogen and progestin independently control the synthesis of transcripts arising from the PR promoters and that estrogen alters the cellular PR A/B ratio provides possible mechanisms underlying the cell and tissue specificity of PR regulation.
人孕酮受体（PR）的表达受两个启动子区域调控，产生编码PR A和B蛋白的转录本。尚不清楚PR表达的主要生理调节因子雌激素和孕酮是否对PR启动子产生同等作用。本研究的目的是分析雌激素和孕激素对T-47D人乳腺癌细胞中PR启动子、PR编码转录本以及PR A和B蛋白的影响。孕激素ORG 2058导致PR基因转录长期减少，同时也消除了雌激素对PR转录的刺激作用。雌二醇（E2）处理增加了转染到T-47D细胞中的B启动子的活性，但未增加A启动子的活性。ORG 2058对任一启动子的基础活性或E2刺激的活性均无影响。E2导致源自启动子B的转录本优先增加，而孕激素降低了所有PR转录本的水平。E2优先增加PR B蛋白的浓度，并导致PR A/B比值降低。这表明雌激素和孕激素独立控制源自PR启动子的转录本的合成，且雌激素改变细胞PR A/B比值，为PR调节的细胞和组织特异性提供了可能的机制。
