Farnell Yuhua Z, Ing Nancy H
Departments of Animal Science, Faculty of Genetics, Texas A&M University, College Station, TX 77843-2471, USA.
J Steroid Biochem Mol Biol. 2003 Mar;84(4):453-61. doi: 10.1016/s0960-0760(03)00066-9.
The purpose of this study was to identify an endometrial cell line that maintained the E2 up-regulation of estrogen receptor (ER) mRNA by enhanced message stability and to assess its dependence on ER protein. Estradiol (E2) effects on gene expression were measured in three cell lines: one immortalized from sheep endometrial stroma (ST) and two from human endometrial adenocarcinomas (Ishikawa and ECC-1). E2 up-regulated ER mRNA levels in ST and Ishikawa cells, but down-regulated ER mRNA levels in ECC-1 cells. E2 up-regulated progesterone receptor (PR), glyceraldehyde 3-phosphate dehydrogenase (GAPDH), and transforming growth factor-alpha (TGF-alpha) in both Ishikawa and ECC-1 cells. The selective estrogen receptor modulator ICI 182,780 antagonized the E2-induced up-regulation of ER and/or PR mRNA levels in all three cells, while another, GW 5638, antagonized the up-regulation of PR mRNA in Ishikawa and ECC-1 cells. In mechanistic studies, E2 had no effect on ER mRNA stability in ST cells and it destabilized ER mRNA in ECC-1 cells. Thus, Ishikawa cells appear to be the most physiologically relevant cell line in which to study the up-regulation of ER mRNA levels by enhanced mRNA stability. Its antagonism by ICI 182,780 reveals that ER protein is involved in this E2 response.
本研究的目的是鉴定一种子宫内膜细胞系，该细胞系通过增强信息稳定性维持雌激素受体（ER）mRNA的E2上调，并评估其对ER蛋白的依赖性。在三种细胞系中测量了雌二醇（E2）对基因表达的影响：一种是从绵羊子宫内膜基质永生化而来的（ST），另外两种是从人子宫内膜腺癌而来的（Ishikawa和ECC-1）。E2上调了ST和Ishikawa细胞中ER mRNA的水平，但下调了ECC-1细胞中ER mRNA的水平。E2上调了Ishikawa和ECC-1细胞中的孕激素受体（PR）、甘油醛-3-磷酸脱氢酶（GAPDH）和转化生长因子-α（TGF-α）。选择性雌激素受体调节剂ICI 182,780拮抗了E2诱导的所有三种细胞中ER和/或PR mRNA水平的上调，而另一种GW 5638拮抗了Ishikawa和ECC-1细胞中PR mRNA的上调。在机制研究中，E2对ST细胞中ER mRNA的稳定性没有影响，而使ECC-1细胞中的ER mRNA不稳定。因此，Ishikawa细胞似乎是研究通过增强mRNA稳定性上调ER mRNA水平的最具生理相关性的细胞系。ICI 182,780对其的拮抗作用表明ER蛋白参与了这种E2反应。
