Differential regulation of gene expression by estrogen in estrogen growth-independent and -dependent MCF-7 human breast cancer cell sublines.
Differential regulation of gene expression by estrogen in estrogen growth-independent and -dependent MCF-7 human breast cancer cell sublines.
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DOI：
10.1210/mend-5-9-1323
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发表时间：
1991-09
影响因子：
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通讯作者：
Hyeseong Cho;Peter A. Ng;B. Katzenellenbogen
中科院分区：
文献类型：
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作者：
Hyeseong Cho;Peter A. Ng;B. Katzenellenbogen
我们研究了雌二醇（E2）调节三种mrna表达的能力[pS2，孕激素受体（PR）和雌激素受体（ER）]，已知在亲代E2生长响应的MCF-7细胞中受E2调控，在E2生长不依赖的MCF-7 K3中)，之前从亲代雌激素依赖的MCF-7 K1人乳腺癌细胞中分离出来，在体外长期生长缺乏雌激素。在体外获得不依赖雌激素的生长，以及在没有雌激素的裸鼠体内形成肿瘤的能力。我们发现pS2 mRNA的含量和pS2基因的转录率，虽然在MCF-7 K1细胞中E2显着增加，但在该亚系中E2不再刺激pS2 mRNA的含量，尽管蛋白激酶激活剂在K1和K3细胞中都显著增加（大于10倍）pS2 mRNA。事实上，在MCF-7 K3细胞中，基础pS2 mRNA水平升高了2.8 +/- 0.4倍，E2引起pS2 mRNA水平的浓度依赖性抑制。相反，与亲本K1细胞一样，K3亚系中的PR mRNA仍然被E2上调，ER mRAN含量和ER mRNA转录率仍然被E2下调，并表现出正常的E2剂量-反应关系，这表明该亚系中的ER是有功能的。这些结果表明，K3细胞向不依赖雌激素生长的过程伴随着雌激素对一些雌激素诱导基因的调节变化。虽然PR和ER保持正常的E2调控模式，但雌激素生长无关的K3亚群中的pS2基因受到不同程度的影响，不再受到E2的刺激。我们的数据表明，pS2基因调控的改变可能不是由内质网或内质网调控的缺陷引起的。
We have examined the ability of estradiol (E2) to regulate the expression of three mRNAs [for pS2, progesterone receptor (PR), and estrogen receptor (ER)], known to be under E2 regulation in the parental E2 growth-responsive MCF-7 cells, in an E2 growth-independent MCF-7 K3), previously isolated from the parental estrogen-dependent MCF-7 K1 human breast cancer cells after long term growth in vitro in the absence of estrogen, acquired estrogen-independent growth in vitro as well as the ability to form tumors in nude mice in vivo without estrogen. We find that the content of pS2 mRNA and the transcription rate of the pS2 gene, while being markedly increased by E2 in MCF-7 K1 cells, are no longer stimulated by E2 in this subline, although protein kinase activators tremendously increase (greater than 10-fold) pS2 mRNA in both K1 and K3 cells. In fact, basal pS2 mRNA levels are elevated 2.8 +/- 0.4-fold in MCF-7 K3 cells, and E2 evokes a concentration-dependent suppression of the pS2 mRNA level. In contrast, PR mRNA in the K3 subline, as in the parental K1 cells, is still up-regulated by E2, and ER mRAN content and the ER mRNA transcription rate are still down-regulated by E2 and show normal E2 dose-response relationships, implying that the ER in this subline is functional. These results demonstrate that the progression to estrogen-independent growth in K3 cells is accompanied by a change in the regulation of some estrogen-induced genes by estrogen. While PR and ER retain normal patterns of regulation by E2, the pS2 gene in the estrogen growth-independent K3 subline is differentially affected and is no longer stimulated by E2. Our data suggest that this altered regulation of the pS2 gene is probably not caused by a defect of the ER or ER regulation in this subline.