REGULATION OF PROGESTERONE-RECEPTOR MESSENGER RIBONUCLEIC-ACID AND PROTEIN-LEVELS IN MCF-7 CELLS BY ESTRADIOL - ANALYSIS OF ESTROGENS EFFECT ON PROGESTERONE-RECEPTOR SYNTHESIS AND DEGRADATION
REGULATION OF PROGESTERONE-RECEPTOR MESSENGER RIBONUCLEIC-ACID AND PROTEIN-LEVELS IN MCF-7 CELLS BY ESTRADIOL - ANALYSIS OF ESTROGENS EFFECT ON PROGESTERONE-RECEPTOR SYNTHESIS AND DEGRADATION
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DOI：
10.1210/endo-122-3-935
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发表时间：
1988-03-01
期刊：
影响因子：
4.8
通讯作者：
KATZENELLENBOGEN, BS
中科院分区：
文献类型：
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作者：
NARDULLI, AM;GREENE, GL;KATZENELLENBOGEN, BS
人乳腺癌细胞系MCF-7对雌激素的反应是孕酮受体（PR）水平升高。在这项研究中，我们使用密集的氨基酸密度变化分析，直接解决的问题，雌激素是否增加乳腺癌细胞MCF-7细胞中的PR水平，通过改变受体的合成和/或降解率。使用不同浓度的雌二醇（E2），其达到一半最大值（3 × 10 - 6）的PR水平。10-11 M E2）或最大值（6 × 10 - 11 M E2）。10-11 M E2），我们已经使用密集（15 N，13 C，2 H）氨基酸掺入进行了蔗糖梯度密度位移分析，以研究PR合成和降解速率。这些研究揭示了预先存在的正常密度受体随时间的非线性损失。从动力学建模分析，等效降解率估计PR是否维持最大或半最大水平，表明E2对PR含量的主要影响是增加PR合成速率，同时保持降解速率不变。E2刺激的PR蛋白的增加也与PR mRNA水平的增加有关，如通过使用人PR cDNA探针所证明的。密度偏移数据提供了证据，表明MCF-7细胞中雌激素暴露后PR水平的增加是受体合成速率增加的结果，而不是受体降解速率的调节。
The human breast cancer cell line MCF-7 responds to estrogens with increased progesterone receptor (PR) levels. In this study, we use dense amino acid density shift analyses to address directly the question of whether estrogen increases PR levels in MCF-7 cells by altering rates of receptor synthesis and/or degradation. Using different concentrations of estradiol (E2), which achieve PR levels that are half-maximal (3 .times. 10-11 M E2) or maximal (6 .times. 10-11 M E2), we have done sucrose gradient density shift analyses using dense (15N, 13C, 2H) amino acid incorporation to study rates of PR synthesis and degradation. These studies reveal a nonlinear loss of preexisting normal density receptor with time. From kinetic modeling analyses, equivalent rates of degradation are estimated for PR whether maximal or half-maximal levels are maintained, indicating that the major effect of E2 on PR content is to increase the rate of PR synthesis while leaving the degradation rate unaltered. The E2-stimulated increase in PR protein is also associated with increased levels of PR mRNA, as demonstrated by the use of a human PR cDNA probe. The density shift data provide evidence that the increased PR levels after estrogen exposure in MCF-7 cells are the result of an increased rate of receptor synthesis, rather than modulation of the rate of receptor degradation.