scholarly journals The Human Brain Has Distinct Regional Expression Patterns of Estrogen Receptor α mRNA Isoforms Derived from Alternative Promoters

2002 ◽  
Vol 75 (4) ◽  
pp. 1390-1397 ◽  
Author(s):  
Marie K. Österlund ◽  
Kaj Grandien ◽  
Eva Keller ◽  
Yasmin L. Hurd
2005 ◽  
Vol 186 (1) ◽  
pp. 51-60 ◽  
Author(s):  
J Varayoud ◽  
J G Ramos ◽  
L Monje ◽  
V Bosquiazzo ◽  
M Muñoz-de-Toro ◽  
...  

The gene for estrogen receptor α (ERα) has been shown to be under complex hormonal control and its activity can be regulated by mRNA alternative splicing. Here we examined the regulation of ERα transcription and translation in the rat uterus by ovarian steroid hormones. We examined whether expression of ERα mRNA splice isoforms is hormonally regulated in ovariectomized (OVX) and cycling rats. Adult OVX female rats were treated daily with 17-β estradiol (E2) (0.05 μg/rat or 5 μg/rat), progesterone (P4) (1 mg/rat) or a combination of both hormones for 4 days. Animals were killed 24 h after the last injection and uterine horns were removed. In order to determine whether ERα mRNA isoforms are differentially expressed under various physiological conditions, animals were evaluated at proestrus, estrus and diestrus. The ERα protein and mRNA were detected by immunohistochemistry and comparative RT-PCR analysis respectively. The presence of ERα mRNA isoforms was evaluated using a nested RT-PCR assay. In OVX control rats, ERα mRNA and protein levels were high, demonstrating a constitutive expression of the ERα gene in the uterus. When animals received P4 or the high dose of E2, a significant decrease in both ERα mRNA and protein was observed in the uterus. However, when rats were protein was treated with the low dose of E2, only the ERα down-regulated; no changes were observed in ERα mRNA expression. In addition to the full-length ERα mRNA, OVX control rat uteri expressed three shorter transcripts: Σ3, Σ4 and Σ3,4 (lacking exon 3, exon 4, or both 3 and 4 respectively). Surprisingly, when OVX animals were treated with P4, the low dose of E2 or a combination of both steroids, expression of the Σ3 isoform was completely abolished. During the estrous cycle, all ERα mRNA splicing variants were detected at proestrus and estrus. However, in diestrus, significant low levels of the Σ3 isoform were observed. In summary, our results suggest a dose-dependent relationship between E2 concentrations and the level of control in the ERα transcription–translation cascade. Moreover, the alternative splicing of the ERα primary transcript is influenced by the hormonal milieu, suggesting that these events could affect the estrogen responsiveness of the rat uterus during the estrous cycle.


2008 ◽  
Vol 24 (2) ◽  
pp. 93-98 ◽  
Author(s):  
Tatjana A. Ishunina ◽  
Dick F. Swaab

2012 ◽  
Vol 20 (1) ◽  
pp. 91-102 ◽  
Author(s):  
Yumi Endo ◽  
Tatsuya Toyama ◽  
Satoru Takahashi ◽  
Nobuyasu Yoshimoto ◽  
Mai Iwasa ◽  
...  

Recent analyses have identified heterogeneity in estrogen receptor α (ERα)-positive breast cancer. Subtypes called luminal A and luminal B have been identified, and the tumor characteristics, such as response to endocrine therapy and prognosis, are different in these subtypes. However, little is known about how the biological characteristics of ER-positive breast cancer are determined. In this study, expression profiles of microRNAs (miRNAs) and mRNAs in ER-positive breast cancer tissue were compared between ERhighKi67lowtumors and ERlowKi67hightumors by miRNA and mRNA microarrays. Unsupervised hierarchical clustering analyses revealed distinct expression patterns of miRNAs and mRNAs in these groups. We identified a downregulation of miR-1290 in ERhighKi67lowtumors. Among 11 miRNAs that were upregulated in ERhighKi67lowtumors, quantitative RT-PCR detection analysis using 64 samples of frozen breast cancer tissue identified six miRNAs (let-7a, miR-15a, miR-26a, miR-34a, miR-193b, and miR-342-3p). We picked up 11 genes that were potential target genes of the selected miRNAs and that were differentially expressed in ERhighKi67lowtumors and ERlowKi67hightumors. Protein expression patterns of the selected target genes were analyzed in 256 ER-positive breast cancer samples by immunohistochemistry: miR-1290 and its putative targets,BCL2, FOXA1, MAPT, andNAT1, were identified. Transfection experiments revealed that introduction of miR-1290 into ER-positive breast cancer cells decreased expression of NAT1 and FOXA1. Our results suggest that miR-1290 and its potential targets might be associated with characteristics of ER-positive breast cancer.


Cancers ◽  
2021 ◽  
Vol 13 (10) ◽  
pp. 2355
Author(s):  
Mara H. O’Brien ◽  
Henry C. Pitot ◽  
Sang-Hyuk Chung ◽  
Paul F. Lambert ◽  
Norman R. Drinkwater ◽  
...  

Estrogen protects females from hepatocellular carcinoma (HCC). To determine whether this protection is mediated by classic estrogen receptors, we tested HCC susceptibility in estrogen receptor-deficient mice. In contrast to a previous study, we found that diethylnitrosamine induces hepatocarcinogenesis to a significantly greater extent when females lack Esr1, which encodes Estrogen Receptor-α. Relative to wild-type littermates, Esr1 knockout females developed 9-fold more tumors. Deficiency of Esr2, which encodes Estrogen Receptor-β, did not affect liver carcinogenesis in females. Using microarrays and QPCR to examine estrogen receptor effects on hepatic gene expression patterns, we found that germline Esr1 deficiency resulted in the masculinization of gene expression in the female liver. Six of the most dysregulated genes have previously been implicated in HCC. In contrast, Esr1 deletion specifically in hepatocytes of Esr1 conditional null female mice (in which Cre was expressed from the albumin promoter) resulted in the maintenance of female-specific liver gene expression. Wild-type adult females lacking ovarian estrogen due to ovariectomy, which is known to make females susceptible to HCC, also maintained female-specific expression in the liver of females. These studies indicate that Esr1 mediates liver cancer risk, and its control of sex-specific liver gene expression involves cells other than hepatocytes.


Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4144-4159 ◽  
Author(s):  
B. P. Huderson ◽  
T. T. Duplessis ◽  
C. C. Williams ◽  
H. C. Seger ◽  
C. G. Marsden ◽  
...  

Elevated phosphorylation of estrogen receptor α (ERα) at serines 118 (S118) and 167 (S167) is associated with favorable outcome for tamoxifen adjuvant therapy and may serve as surrogate markers for a functional ERα signaling pathway in breast cancer. It is possible that loss of phosphorylation at S118 and/or S167 could disrupt ERα signaling, resulting in aggressive ERα-independent breast cancer cells. To this end, MCF-7 breast cancer cells were stably transfected with an ERα-specific short hairpin RNA that reduced endogenous ERα. The resulting cell line was stably transfected with wild-type ERα (ER-AB cells), or ERα containing serine to alanine mutation at S118 or S167 (S118A cells and S167A cells, respectively). These stable cell lines expressed approximately equivalent ERα compared with parental MCF-7 cells and were evaluated for growth, morphology, migration/invasion, and ERα-regulated gene expression. S118A cells and S167A cells exhibited increased growth and migration/invasion in vitro. Forward- and side-scatter flow cytometry revealed that S167A cells were smaller in size, and both S118A and S167A cells exhibited less cellular complexity. S118A and S167A cells expressed pancytokeratin and membrane localization of β-catenin and did not express vimentin, indicating retention of epithelial lineage markers. Expression of ERα-target genes and other genes regulated by ERα signaling or involved in breast cancer were markedly altered in both S118A and S167A cells. In summary, attenuated phosphorylation of ERα at S118 and S167 significantly affected cellular physiology and behavior in MCF-7 breast cancer cells, resulting in increased growth, migration/invasion, compromised expression of ERα target genes, and markedly altered gene expression patterns.


2005 ◽  
Vol 17 (2) ◽  
pp. 212
Author(s):  
B.-K. Kim ◽  
H.J. Chung ◽  
Y.G. Ko ◽  
Y.M. Kim ◽  
H.-H. Seong ◽  
...  

Although the expression of important genes in the embryo at pre-implantation stage, which encompasses the period from fertilization to implantation, have been reported for mice and cows, little information relevant to this subject is known in pigs. The objective of this study was to investigate the changes of importantly expressed genes and proteins in endometrial tissue of pigs from fertilization to implantation. Six genes, including estrogen receptor-α, estrogen receptor-β, LIF, LR (LIF receptor), TGFβ1, and TGFβ2, that may play important roles in regulating uterine receptivity and successful implantation and that show different expression patterns by the stages of pregnancy were selected. As a step toward understanding the role of gene and protein expression changes in endometrial tissue of pigs during the preimplantation stage (Day 2, Day 6, Day 8, Day 12, and Day 17, n = 3/group) and the post-implantation stage (Day 21 and Day 33, n = 3/group) and Day 0 (estrous), real-time PCR methods for quantitative analysis of genes and immunohistochemistry methods to localize protein expression were utilized. Data from quantitative real-time PCR were analyzed by ANOVA. The results of this experiment indicated that estrogen receptor-β mRNA level was sharply increased to Day 12 of pregnancy, while estrogen receptor-α mRNA did not change drastically during early pregnancy stage. In contrast, levels of LIF and LR mRNA were increased from Day 2 to Day 33. Although TGFβ1 mRNA reached peak on Day 17 and TGFβ2 mRNA showed the highest level on Day 17, TGFβ2 did not appear to change drastically. For the protein expression patterns, estrogen receptor-α and estrogen receptor-β proteins were expressed in both luminal epithelium and glandular epithelium, but they were only partially expressed in some tissues of stroma cells. LIF protein was expressed in all cell types, while TGF β1 protein was high expressed in glandular epithelium. Also, ERs, LIF, and TGF β1 mRNA and protein expression showed stage- and cell-specific expression patterns. We also investigated the gene expression of TGF β1 mRNA and TGF β2 mRNA in early conceptus (Day 12 and Day 17). TGF β1 mRNA expression was low in Day 12 embryos, and increased progressively to Day 17. This indicated that both the maternal uterus and the conceptus represent the same gene expression pattern. These results suggest that estrogen receptor-β could be an important factor in estrogen action in endometrial tissue during early gestation in pigs, and TGF βs function in both autocrine and paracrine interactions. Progressive increase in TGF β1 mRNA expression in conceptus and uterine tissues suggest important roles of TGF β1 in conceptus development and establishment of the uterine receptivity during the peri-implantation period.


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