Estradiol up-regulates estrogen receptor messenger ribonucleic acid in endometrial carcinoma (Ishikawa) cells by stabilizing the message

Abstract

Estrogens up-regulate expression of the estrogen receptor alpha (ER) gene in most mammalian tissues studied. Using the ovariectomized ewe as a model, we determined that estradiol (E 2 ) acted post-transcriptionally to increase endometrial ER mRNA concentrations by enhancing the stability of the message. The purpose of this study was to determine whether a similar E 2 effect occurs in Ishikawa cells, a well-differentiated human endometrial adenocarcinoma cell line. The presence and function of ER protein in Ishikawa cells was demonstrated by transactivation of a transfected plasmid (ERE 2 tkCAT) in response to 10 −9 M E 2 , resulting in a 550% increase in reporter gene RNA. Ishikawa cells also responded to E 2 by up-regulating their ER mRNA concentration an average of 100% between 7 and 24 h of treatment. The effect of E 2 on ER mRNA stability was measured after blocking transcription with actinomycin D to find that the half-life increased from 6 to 10 h in control and E 2 -treated cells respectively. These results are consistent with cell-free studies which showed significant enhancement of the half-life of radiolabeled ER 3′ untranslated region (3′UTR) RNA in extracts from E 2 -treated cells versus those from control cells. Thus, Ishikawa cells provide a relevant model system for the study of E 2 -regulated endometrial gene expression.

Molecular cloning, expression, and regulation of estrogen receptors in pigeon oviduct epithelial cells

“…In vivo, ovine uterine cells responded to estrogen treatment by up-regulating the transcription of ERa mRNA (Ing and Tornesi, 1997;Robertson et al, 2001). Estrogen also increased ERa mRNA levels in ZR-75 (Clayton et al, 1997) and Ishikawa cells (Robertson et al, 2002). However, estrogen treatment decreased ERa mRNA in ECC-1 (Farnell and Ing, 2003) and MCF-7 cells (Saceda et al, 1998).…”

“…The ability of estrogen to modulate ERα expression has been most extensively studied in cell lines (Treilleux et al, 1997;Robertson et al, 2002). One hypothesis suggests that estrogen induces trans-acting factors to bind to specific elements of ER mRNA molecules, and protects their ends.…”

Estrogen Upregulates Cyclic AMP Response Element Modulator α Expression and Downregulates Interleukin-2 Production by Human T Lymphocytes

“…Indeed, a preferential expression of CREMα over the alternatively spliced isoform CREMtau2α is seen progressively within the myometrium from nonpregnant to pregnant and laboring stages, and this switch is mediated by the splicing factor SRp40 (24). β-Estradiol has also been shown to increase ER expression by stabilizing its mRNA (27). The estrogen-initiated suppression of IL-2 production ( Figure 5) may contribute to the pathogenesis of SLE, since it is clear that IL-2 is needed for the generation of cytotoxic responses, the generation of T regulatory cells and activationinduced cell death.…”

Ishikawa cells exhibit differential gene expression profiles in response to oestradiol or 4-hydroxytamoxifen

“…In addition, the proliferative response of endometrial cells in culture to SERMs has been shown to be variable, largely due to conditional differences between dose, time of exposure or media components (Shah et al 2004). In this study, we used an established human uterine-derived epithelial cell line (Ishikawa; (Anzai et al 1989)), which is oestrogen-responsive (Holinka et al 1986, Robertson et al 2002 and shares many phenotypic features in common with normal human endometrial epithelial cells (Lessey et al 1996) to investigate the variation and extent of gene expression changes following tamoxifen treatment. Global gene expression profiles were determined and compared following treatment with 4-hydroxytamoxifen (OHT, 10 K6 M) or 17b-oestradiol (E 2 , 10 K8 M).…”