Response element sequence modulates estrogen receptor alpha and beta affinity and activity

Kulakosky, PC; McCarty, MA; Jernigan, S C; Risinger, K E; Klinge, Carolyn M.

doi:10.1677/jme.0.0290137

Cited by 47 publications

(40 citation statements)

References 55 publications

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“…Further, EREs in which nucleotides are altered in both arms of the palindrome show lower transcriptional activity than those containing alterations in only one ERE half-site (Klinge 2001). These results have been confirmed experimentally (Driscoll et al 1998, Tyulmenkov & Klinge 2000a, 2001a,b, Tyulmenkov et al 2000, Kulakosky et al 2002. Lefstin & Yamamoto (1998) proposed that response elements recognized by nuclear transcription factors, including members of the steroid/ nuclear receptor superfamily, contain information that is interpreted by bound regulator factors.…”

Section: Introductionmentioning

confidence: 79%

Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

Klinge¹,

Jernigan²,

Mattingly³

et al. 2004

Journal of Molecular Endocrinology

179

130

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One mechanism by which ligand-activated estrogen receptors and (ER and ER ) stimulate gene transcription is through direct ER interaction with specific DNA sequences, estrogen response elements (EREs). ERE-bound ER recruits coactivators that stimulate gene transcription. Binding of ER to natural and synthetic EREs with different nucleotide sequences alters ER binding affinity, conformation, and transcriptional activity, indicating that the ERE sequence is an allosteric effector of ER action. Here we tested the hypothesis that alterations in ER conformation induced by binding to different ERE sequences modulates ER interaction with coactivators and corepressors. CHO-K1 cells transfected with ER or ER show ERE sequence-dependent differences in the functional interaction of ER and ER with coactivators steroid receptor coativator 1 (SRC-1), SRC-2 (glucocorticoid receptor interacting protein 1 (GRIP1)), SRC-3 amplified in breast cancer 1 (AIB1) and ACTR, cyclic AMP binding protein (CBP), and steroid receptor RNA activator (SRA), corepressors nuclear receptor co-repressor (NCoR) and silencing mediator for retinoid and thyroid hormone recpetors (SMRT), and secondary coactivators coactivator associated arginine methyltransferase 1 (CARM1) and protein arginine methyltransferase 1 (PRMT1). We note both ligand-independent as well estradiol-and 4-hydroxytamoxifen-dependent differences in ER-coregulator activity. In vitro ER-ERE binding assays using receptor interaction domains of these coregulators failed to recapitulate the cell-based results, substantiating the importance of the full-length proteins in regulating ER activity. These data demonstrated that the ERE sequence impacts estradioland 4-hydroxytamoxifen-occupied ER and ER interaction with coregulators as measured by transcriptional activity in mammalian cells.

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Section: Introductionmentioning

confidence: 79%

Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

Klinge¹,

Jernigan²,

Mattingly³

et al. 2004

Journal of Molecular Endocrinology

179

130

View full text Add to dashboard Cite

show abstract

“…To determine ERa and ERb protein expression, known concentrations, as assayed by [ 3 H]E 2 binding (Kulakosky et al 2002), of baculovirus-expressed rhERa and rhERb protein were separated in parallel with the WCEs of the lung adenocarcinoma cell lines and used as calibrators to estimate ERa and ERb expression levels by Western blot (Fig. 3B-E).…”

Section: Resultsmentioning

confidence: 99%

“…Protein concentrations were determined using BioRad's DCC assay (Hercules, CA, USA). (Kulakosky et al 2002, Kulakosky & Klinge 2003 or to the NE, CE and WCE from the lung cell lines was measured in the presence of 200-fold molar excess of 'cold' E 2 by adsorption to hydroxyapatite (HAP) as previously described (Kulakosky et al 2002).…”

Section: Rna Extraction and Quantitative Real Time Rt-pcrmentioning

confidence: 99%

“…As positive and negative controls, known amounts (in fmoles from HAP assays) of baculovirus-expressed rhERa and rhERb, purchased from Panvera or produced in Sf21 cells (Kulakosky et al 2002, Kulakosky & Klinge 2003 were separated in parallel with WCE samples. The transfer was monitored by pre-stained molecular weight markers (Precision Standard, BioRad).…”

Section: Western Blottingmentioning

confidence: 99%

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Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells

Dougherty¹,

Mazhawidza²,

Bohn³

et al. 2006

Endocr Relat Cancer

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The higher frequency of lung adenocarcinoma in women smokers than in men smokers suggests a role for gender-dependent factors in the etiology of lung cancer. We evaluated estrogen receptor (ER) a and b expression and activity in human lung adenocarcinoma cell lines and normal lung fibroblasts. Full-length ERa and ERb proteins were expressed in all cell lines with higher ERb than ERa. Although estradiol (E 2 ) binding was similar, E 2 stimulated proliferation only in cells from females, and this response was inhibited by anti-estrogens 4-hydroxytamoxifen (4-OHT) and ICI 182,780. In contrast, E 2 did not stimulate replication of lung adenocarcinoma cells from males and 4-OHT or ICI did not block cell proliferation. Similarly, transcription of an estrogen response element-driven reporter gene was stimulated by E 2 in lung adenocarcinoma cells from females, but not males. Progesterone receptor (PR) expression was increased by E 2 in two out of five adenocarcinoma cell lines from females, but none from males. E 2 decreased E-cadherin protein expression in some of the cell lines from females, as it did in MCF-7 breast cancer cells, but not in the cell lines from males. Thus, ERa and ERb expression does not correlate with the effect of ER ligands on cellular activities in lung adenocarcinoma cells. On the other hand, coactivator DRIP205 expression was higher in lung adenocarcinoma cells from females versus males and higher in adenocarcinoma cells than in normal human bronchial epithelial cells. DRIP205 and other ER coregulators may contribute to differences in estrogen responsiveness between lung adenocarcinoma cells in females and males.

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“…SIAH2 belongs to the genes of the ER-positive epithelial breast cancer subtype and strongly associated with ER levels [3,4], and it was overexpressed in malignant compared with normal breast tissue [5]. Moreover, SIAH2 (AC011317; 147 kb) sequence analysis revealed an estrogen response element (CAGGTCA NNNTGACCTG) [6] in the intron between exon 1 and 2.…”

Section: Introductionmentioning

confidence: 99%

Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to endocrine therapy in breast cancer

Jansen

Ruigrok-Ritstier

Dorssers

et al. 2008

Breast Cancer Res Treat

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International audienceIn our microarray analysis we observed that Seven-in-Absentia Homolog 2 (SIAH2) levels were low in estrogen receptor (ER) positive breast tumors of patients resistant to first-line tamoxifen therapy. The aim of this study was to evaluate SIAH2 for its (a) predictive/prognostic value, and (b) functional role in endocrine therapy resistance. SIAH2 expression was measured with quantitative Real-Time-PCR (qRT-PCR) in 1205 primary breast tumor specimens and related to disease outcome. The functional role of SIAH2 was determined in human breast cancer cell lines ZR-75-1, ZR/HERc, and MCF7. Cell lines were treated with estrogen (E2), anti-estrogen ICI164.384 or epidermal growth factor (EGF). Moreover, MCF7 was treated with ICI164.384 after silencing SIAH2 expression. SIAH2 was not prognostic in 603 lymph node negative patients who had not received adjuvant systemic therapy. In multivariate analysis of ER-positive tumors of 235 patients with recurrent disease, SIAH2 as continuous variable, significantly predicted first-line tamoxifen treatment failure (OR = 1.48; = 0.05) and progression-free survival (PFS) (HR = 0.79; = 0.007). Furthermore, in primary breast cancer patients treated with adjuvant tamoxifen, SIAH2 predicted metastasis-free survival (MFS) (HR = 0.73; = 0.005). In vitro experiments showed that SIAH2 silencing in MCF7 cells resulted in resistance to ICI164.384-treatment when compared with mock silenced cells ( = 0.008). Interestingly, in ZR cells transfected with EGFR (ZR/HERc), SIAH2 expression was induced by E2 but downregulated by EGF. In primary breast tumor specimens as well as in vitro low SIAH2 levels associated with resistance to endocrine therapy. Moreover, SIAH2 expression showed an opposite regulation by E2 and EGF

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Response element sequence modulates estrogen receptor alpha and beta affinity and activity

Cited by 47 publications

References 55 publications

Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

Estrogen response element-dependent regulation of transcriptional activation of estrogen receptors α and β by coactivators and corepressors

Gender difference in the activity but not expression of estrogen receptors α and β in human lung adenocarcinoma cells

Downregulation of SIAH2, an ubiquitin E3 ligase, is associated with resistance to endocrine therapy in breast cancer

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