The effects of estradiol and selective estrogen receptor modulators on gene expression and messenger RNA stability in immortalized sheep endometrial stromal cells and human endometrial adenocarcinoma cells.
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.
Departments of Animal Science, Faculty of Genetics, Texas A&M University, College Station, TX 77843-2471, USA.
Yuhua Z
YZ
Farnell
Nancy H
NH
Ing
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000378:metabolism*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology; D015152:Blotting, Northern; D002478:Cells, Cultured; D003001:Cloning, Molecular; D015536:Down-Regulation; D016889:Endometrial Neoplasms / Q000188:drug therapy*; D004717:Endometrium / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D005260:Female; D000077267:Fulvestrant; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012333:RNA, Messenger / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D020845:Selective Estrogen Receptor Modulators / Q000494:pharmacology*; D012756:Sheep; D017154:Stromal Cells / Q000187:drug effects*; D013997:Time Factors; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
D018931:Antineoplastic Agents, Hormonal; D004965:Estrogen Antagonists; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D020845:Selective Estrogen Receptor Modulators; D016211:Transforming Growth Factor alpha; D000077267:Fulvestrant; D004958:Estradiol