Saceda M, Lippman M E, Chambon P, Lindsey R L, Ponglikitmongkol M, Puente M, Martin M B
Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Mol Endocrinol. 1988 Dec;2(12):1157-62. doi: 10.1210/mend-2-12-1157.
The role of estradiol in the regulation of its cognate receptor in MCF-7 cells was investigated in this study. After treatment with 10(-9) M estradiol, the level of receptor protein was measured using an enzymeimmunoassay. By 6 h, the receptor protein declined by about 60% from a level of approximately 3.6 to 1.2 fmol/micrograms DNA. The level of receptor remained suppressed for 24-48 h. Similar results were obtained with an estrogen receptor (ER) binding assay. The steady state level of ER mRNA was determined by an RNase protection assay. Estrogen treatment resulted in a maximum suppression of mRNA by 6 h. Receptor mRNA remained depressed for 48 h. Transcription run on experiments demonstrated a transient decrease of about 90% in ER transcription after 1 h. By 3-6 h transcription increased approximately 2-fold and remained elevated for at least 48 h. These data suggest that estrogen down-regulates ER mRNA by inhibition of ER gene transcription at early times and by a posttranscriptional effect on receptor mRNA at later times.
本研究探讨了雌二醇在MCF-7细胞中对其同源受体的调节作用。用10(-9)M雌二醇处理后，采用酶免疫分析法测定受体蛋白水平。到6小时时，受体蛋白从约3.6 fmol/μg DNA的水平下降了约60%，降至1.2 fmol/μg DNA。受体水平在24至48小时内一直受到抑制。雌激素受体（ER）结合试验也得到了类似结果。通过核糖核酸酶保护试验测定ER mRNA的稳态水平。雌激素处理6小时后导致mRNA最大程度的抑制。受体mRNA在48小时内一直处于低水平。转录实验表明，1小时后ER转录瞬时下降约90%。到3至6小时，转录增加约2倍，并至少持续升高48小时。这些数据表明，雌激素在早期通过抑制ER基因转录而下调ER mRNA，在后期则通过对受体mRNA的转录后作用来下调。
