Estradiol stimulates expression of two human prolactin receptor isoforms with alternative exons-1 in T47D breast cancer cells.
Estradiol stimulates expression of two human prolactin receptor isoforms with alternative exons-1 in T47D breast cancer cells.
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雌二醇刺激 T47D 乳腺癌细胞中两种具有替代外显子 1 的人催乳素受体亚型的表达。
DOI：
10.1016/s0960-0760(02)00184-x
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Dufau,MariaL
中科院分区：
文献类型：
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作者：
Leondires,MarkP;Hu,ZhangZhi;Dong,Juying;Tsai-Morris,ChonHwa;Dufau,MariaL
人催乳素受体 (hPRLR) 的表达在体内动物组织中以及在体外正常人子宫内膜细胞和 MCF7 人乳腺癌细胞中受雌二醇-17β (E2) 调节。本研究的目的是确定 E2 对最近描述的两种具有不同外显子 1、hE13 和 hE1N1 的 hPRLR 亚型表达的影响，它们分别从通用 hPIII 启动子（也存在于大鼠和小鼠中）和人类特异性启动子 hPN1 转录。此外，还确定雌二醇对癌细胞中 hPIII 启动子活性的影响。在存在或不存在 E2 受体拮抗剂 ICI 182,780 的情况下与 E2 一起孵育后，使用定量竞争性 RT-PCR 检查 T47D 乳腺癌细胞的两种替代非编码外显子 1 转录物 hE13 和 hE1N1 的表达水平。还在用 hPIII 启动子荧光素酶报告基因构建体瞬时转染的细胞中评估了雌二醇的作用。 E2显着增加hPRLR mRNA转录物hE13和hE1N1的表达。在转染研究中，E2 激活 hPIII 启动子。雌二醇的这种作用可通过与 E2 受体拮抗剂共孵育而显着抑制。我们的结果表明，雌二醇对具有替代外显子 1、hE13 和 hE1N1 的 hPRLR mRNA 种类的表达具有刺激作用，可能是通过激活其相应的启动子来实现的。这些启动子中缺乏正式的 ERE 表明雌二醇的作用是通过激活的 ER 与相关 DNA 结合转因子的结合来介导的。这些发现支持 E2 在人乳腺癌细胞系 hPRLR 表达调节中的作用。
Human prolactin receptor (hPRLR) expression is regulated by estradiol-17β (E2) in vivo in animal tissues, and in vitro in normal human endometrial cells and in MCF7 human breast cancer cells. The objective of this study was to determine the effect of E2on the expression of two recently described hPRLR isoforms with distinct exons-1, hE13and hE1N1that are transcribed from the generic hPIII promoter, also present in the rat and mouse, and the human-specific promoter hPN1, respectively. Also, to determine the effect of estradiol on the hPIII promoter activity in cancer cells. T47D breast cancer cells were examined using quantitative competitive RT-PCR for the level of expression of two alternative non-coding exon-1 transcripts, hE13and hE1N1following incubation with E2in presence or absence of the E2receptor antagonist ICI 182,780. The effects of estradiol were also evaluated in cells transiently transfected with constructs of hPIII promoter luciferase reporter gene. E2significantly increased the expression of both hPRLR mRNA transcripts, hE13and hE1N1. In transfection studies E2activated the hPIII promoter. This effect of estradiol was markedly inhibited by coincubation with the E2receptor antagonist. Our results demonstrate a stimulatory effect of estradiol on the expression of hPRLR mRNA species with alternative exons-1, hE13and hE1N1possibly through activation of their corresponding promoters. The lack of a formal ERE in these promoters suggested that the effect of estradiol is mediated through association of the activated ER with relevant DNA binding transfactor(s). These findings support the role of E2in the regulation of hPRLR expression in human breast cancer cell lines.