Estrogen receptor interaction with estrogen response elements

Klinge, Carolyn M.

doi:10.1093/nar/29.14.2905

Cited by 945 publications

(744 citation statements)

References 191 publications

Supporting

Mentioning

696

Contrasting

Unclassified

Order By: Relevance

“…Sp1, Ap-1) to initiate responsiveness of other target genes (Klinge, 2001;Nilsson et al, 2001). Overall, if we consider that (1) the level of ER protein goes down with E2, Ral and ICI treatments in these cells (Levenson et al, 1998c;Liu et al, 2001) and (2) the Atlas Arrays we used were spotted with PCR-amplified cDNAs for 588 cancer-related genes with a very few E2-responsive genes with putative EREs in their promoter regions, it is fair to say that we are only detecting changes in non-ER-mediated genes.…”

Section: Discussionmentioning

confidence: 99%

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

Levenson¹,

Kliakhandler²,

Svoboda³

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

The purpose of this study was to classify selective oestrogen receptor modulators based on gene expression profiles produced in breast cancer cells expressing either wtERa or mutant 351 ERa. In total, 54 microarray experiments were carried out by using a commercially available Atlas cDNA Expression Arrays (Clontech), containing 588 cancer-related genes. Nine sets of data were generated for each cell line following 24 h of treatment: expression data were obtained for cells treated with vehicle EtOH (Control); with 10 79 or 10 78 M oestradiol; with 10 76 M 4-hydroxytamoxifen; with 10 76 M raloxifene; with 10 76 M idoxifene, with 10 76 M EM 652, with 10 76 M GW 7604; with 5610 75 M resveratrol and with 10 76 M ICI 182,780. We developed a new algorithm 'Expression Signatures' to classify compounds on the basis of differential gene expression profiles. We created dendrograms for each cell line, in which branches represent relationships between compounds. Additionally, clustering analysis was performed using different subsets of genes to assess the robustness of the analysis. In general, only small differences between gene expression profiles treated with compounds were observed with correlation coefficients ranged from 0.83 to 0.98. This observation may be explained by the use of the same cell context for treatments with compounds that essentially belong to the same class of drugs with oestrogen receptors related mechanisms. The most surprising observation was that ICI 182,780 clustered together with oestrodiol and raloxifene for cells expressing wtERa and clustered together with EM 652 for cells expressing mutant 351 ERa. These data provide a rationale for a more precise and elaborate study in which custom made oligonucleotide arrays can be used with comprehensive sets of genes known to have consensus and putative oestrogen response elements in their promoter regions.

show abstract

Section: Discussionmentioning

confidence: 99%

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

Levenson¹,

Kliakhandler²,

Svoboda³

et al. 2002

Br J Cancer

View full text Add to dashboard Cite

show abstract

“…It has been recognized that the conserved sequence of canonical ERE consists of palindromic half-sites interspaced by three nucleotides, namely, 5′-GGTCA-NNN-TGACC-3′ [42]. However, other non-canonical EREs possibly have one or more base aberrations from this sequence [43]. We found a putative ERE (5′-TGTCAGTCTGGCC-3′, −376/−388 bp) in the promoter region of the FPN gene with the software Dragon ERE Finder version 3.0, as previously reported [31] ( Fig.…”

Section: Fpn Transcription Was Regulated By E2 Through a Functional Ementioning

confidence: 99%

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Qian

Yin

Chen

et al. 2015

Cellular Signalling

View full text Add to dashboard Cite

Ferroportin (FPN) is the only known iron exporter in mammalian cells, and is universally expressed in most types of cells. FPN signaling plays a crucial role in maintaining iron homeostasis through governing the level of intracellular iron. Serum iron storage is conversely related with the estrogen level in the female bodies, and women in post-menopause are possibly subjected to iron retention. However, the potential effects of estrogen on iron metabolism are not clearly understood. Here, FPN mRNA transcription in all selected estrogen receptor positive (ER+) cells was significantly reduced upon 17β-estradiol (E2) treatment; and this inhibitory effect could be attenuated by ER antagonist tamoxifen. Likewise, in murine bone marrow-derived macrophages (BMDMs), FPN reduction with elevated intracellular iron (reflected by increased ferritin) was observed in response to E2; however, ferritin level barely responded to E2 in FPN-null BMDMs. The observation of inhibition of FPN mRNA expression was not replicated in ER − cells upon E2. A functional estrogen response element (ERE) was identified within the promoter of FPN, and this ERE was responsible for the suppressive effect of E2 on FPN expression. Moreover, ovariectomized (OVX) and sham-operated (SHAM) mice were used to further confirm the in vitro finding. The expression of hepatic FPN was induced in OVX mice, compared to that in the SHAM mice. Taken together, our results demonstrated that estrogen is involved in regulating FPN expression through a functional ERE on its promoter, providing additional insights into a vital role of estrogen in iron metabolism.

show abstract

“…The consensus sequence of ERE is composed of palindromic half-sites intervened by three nucleotides (5′-GGTCAnnn-TGACC-3′). However, other EREs may have one or more base deviations from this sequence (Klinge, 2001). We identified a potential ERE (5′-AGTCA-GGC-TGTCC-3′, −1244/−1232) in the promoter region of human hepcidin gene using the software Dragon ERE Finder version 3.0 (Bajic et al, 2003) (Fig.…”

Section: Elevated Hepcidin Expression In Liver Devoid Of Endogenous Ementioning

confidence: 99%

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

Hou

Zhang

Wang

et al. 2012

Gene

166

162

View full text Add to dashboard Cite

a b s t r a c t a r t i c l e i n f oIron is essential for the human being, involving in oxygen transport, energy metabolism and DNA synthesis. Iron homeostasis is tightly governed by the hepcidin-ferroportin axis, of which hepcidin is the master regulator. Excess iron is associated with various diseases including osteopenia and osteoporosis, which are closely related to the alternation of the endogenous estrogen level. To verify the biological effect of estrogen on iron metabolism, we established a mouse model of estrogen deficiency by ovariectomy. We demonstrated that the hemoglobin content and serum iron level decreased, whereas the tissue iron level in liver and spleen increased in the ovariectomized mice. Moreover, the transcription of hepatic hepcidin was elevated in ovariectomized mice compared to the control mice. We further demonstrated that there was an estrogen response element (ERE) in the promoter region of the hepcidin gene. The assay using the luciferase reporter system confirmed the existence of a functional ERE in the hepcidin promoter, as the estradiol treatment reduced hepcidin expression in cells transfected with ERE-intact construct, with no response to estradiol in cells transfected with ERE-devoid construct. In conclusion, estrogen greatly contributes to iron homeostasis by regulating hepatic hepcidin expression directly through a functional ERE in the promoter region of hepcidin gene. These findings might help build a better understanding towards the etiology of postmenopausal osteoporosis accompanied by excess tissue iron (such as iron retention of osteoclasts in bone) under estrogen deficiency.

show abstract

Estrogen receptor interaction with estrogen response elements

Cited by 945 publications

References 191 publications

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

Molecular classification of selective oestrogen receptor modulators on the basis of gene expression profiles of breast cancer cells expressing oestrogen receptor α

Estrogen contributes to regulating iron metabolism through governing ferroportin signaling via an estrogen response element

Estrogen regulates iron homeostasis through governing hepatic hepcidin expression via an estrogen response element

Contact Info

Product

Resources

About