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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Estrogen receptor (ER) status in breast cancer is currently the most important predictive biomarker that determines breast cancer prognosis after treatment with endocrine therapy. Although immunohistochemistry has been widely viewed as the gold standard methodology for ER testing in breast cancer, lack of standardized procedures, and lack of regulatory adherence to testing guidelines has resulted in high rates of "false-negative" results worldwide. Standardized testing is only possible after all aspects of ER testing--preanalytical, analytical, and postanalytical, have been closely controlled. A meeting of the "ad-hoc committee" of expert pathologists, technologists, and scientists, representing academic centers, reference laboratories, and various agencies, issued standardization testing recommendations, aimed at optimization of clinical ER testing environment, as a step toward improved standardized testing.
Appl Immunohistochem Mol Morphol 2008 Dec
PMID:Consensus recommendations on estrogen receptor testing in breast cancer by immunohistochemistry. 1893 14

Estrogen receptor (ER)alpha and ERbeta mRNAs levels decreased with clinical stage, myometrial invasion and dedifferentiation. On the other hand, ERRalpha mRNA levels and histoscores increased with clinical stage and myometrial invasion, regardless of dedifferentiation. ERRalpha can bind to the steroid receptor coactivator family without any ligands, and drive transcription activity of the target genes. The competitive interaction of ERRalpha/ER expression associated with the use of common cofactors during loosing estrogen dependency might cause their expression manner. The up-regulation of ERRalpha might be related to tumor growth and advancement in uterine endometrial cancers. It is speculated that ERRalpha is a candidate for prognostic factors in uterine endometrial cancer, although ERRs are not directly related to growth of uterine endometrial cancer.
J Steroid Biochem Mol Biol 2009 Aug
PMID:Clinical implication of estrogen-related receptor (ERR) expression in uterine endometrial cancers. 1941 52

Estrogen receptor (ER)alpha activity is regulated by phosphorylation at several sites. Recently several antibodies specific for individual phosphorylated sites within ERalpha have became available. Validation and use of these antibodies suggests that several forms of phosphorylated ERalpha can be detected in multiple ER+ human breast tumor samples, thus providing relevance for investigating the regulation and function of phosphorylated ERalpha in human breast cancer. Generally, the phosphorylated ERalpha isoforms are associated with parameters that suggest that they are markers of an intact estrogen dependent signaling pathway and better clinical outcome with respect to tamoxifen therapy. Profiling of phosphorylated ERalpha may provide better biomarkers of endocrine therapy response over and above those currently available.
J Steroid Biochem Mol Biol 2009 Mar
PMID:The relevance of phosphorylated forms of estrogen receptor in human breast cancer in vivo. 1942 37

Estrogen receptor (ER)-mediated neuroprotection has been demonstrated in both in vitro and in vivo model systems. Two types of estrogen receptors, ERalpha and ERbeta, are the major mediators of the biological functions of estrogens. In the hippocampus, ERbeta is prevalent over ERalpha. Recently, we reported that during the final phase of lactation there is a neuroprotective mechanism in the hippocampus of the adult female rat against neuronal damage induced by systemic kainic acid administration vs. virgin (metestrus) rats. In this study, we assessed differential ER expression and localization in CA1, CA3 and dentate gyrus regions of dorsal hippocampus of metestrus and lactating adult rats at day 19 of lactation, during basal conditions (metestrus and L19, respectively) and 24h after systemic kainate administration. ERs were assessed by western blot and immunohistochemistry. We found a significant increase in the expression of ERs in the hippocampus during lactation as compared with metestrus. ERbeta was significantly increased in the CA1 and CA3 of lactating rats after the kainic acid insult. In addition, we observed a relocalization of ERbeta from the cytoplasm to the nucleus of neuronal cells. Our results suggest that there is a strong correlation between expression of ERs, especially ERbeta, in lactating CA1 and CA3 hippocampus regions in response to kainate administration, and neuroprotection observed during this reproductive period. This may be one of the mechanisms involved in the protection of the maternal brain to ensure offspring survival.
J Steroid Biochem Mol Biol 2009 Aug
PMID:Estrogen receptors increased expression during hippocampal neuroprotection in lactating rats. 1946 58

Estrogen and selective estrogen receptor modulators (SERMs) differentially impact endometrial cell function, however, the biological basis of these differences is not established. Deregulated cell adhesion to the extracellular matrix, cell movement and invasion are related to endometrial disorders, such as endometriosis or endometrial cancer. Remodeling of the actin cytoskeleton is required to achieve cell adhesion and movement. Estrogen receptor (ER) regulates actin and cell membrane remodeling through extra-nuclear signaling cascades. In this article, we show that administration of 17beta-estradiol (E2) and tamoxifen (TAM) to immortalized Ishikawa endometrial cells or to human endometrial stromal cells (ESC) results in remodeling of actin fibers and cell membrane. This is linked to rapid phosphorylation on Thr(558) of the actin-binding protein moesin and enhanced migration and invasion of normal and Ishikawa cells. Raloxifene (RAL) does not result in moesin activation or actin remodeling. When endometrial cells are exposed to E2 in the presence of TAM or RAL, both SERMs interfere with the recruitment of moesin, with the remodeling of the cytoskeleton, and with cell movement and migration induced by E2. The differential actions of E2, TAM and RAL are linked to a distinct modulation of the extra-nuclear signaling of ER to G proteins and to the Rho-associated kinase. These findings increase our understanding of the actions of estrogen and SERMs in endometrial cells and highlight potential molecular targets to interfere with the estrogen-related altered cell adhesion encountered in endometrial disorders.
Mol Hum Reprod 2009 Oct
PMID:Differential actions of estrogen and SERMs in regulation of the actin cytoskeleton of endometrial cells. 1954

Ductal carcinoma in situ or DCIS belongs to intraductal proliferative lesions, which are a group of cytologically and architecturally diverse ductal proliferations, typically originating from the terminal duct-lobular units. In these intraductal proliferative diseases, estrogens are considered to be involved in the progression of the disease especially from ductal non-neoplastic hyperplasia to DCIS and possibly development of invasive carcinoma from DCIS. Estrogen receptor (ER) alpha is abundantly expressed in atypical ductal hyperplasia and low grade DCIS. Suppression of estrogenic actions using tamoxifen resulted in inhibition of recurrence of DCIS and/or of progression into invasive carcinoma. Intratumoral estrogen concentration in DCIS determined by liquid chromatography/electrospray tandem mass spectrometry is significantly higher than that in non-neoplastic breast tissues with statistically not lower than that in invasive carcinoma. Aromatase mRNA expression in both stromal and parenchymal cells of DCIS determined by quantitative RT-PCR following laser capture microdissection was also much higher than that in non-neoplastic breast, although lower than that in invasive carcinoma. Immunohistochemistry of aromatase also revealed the similar patterns of immunolocalization as in invasive carcinoma. Aromatase is overexpressed in noninvasive breast malignancies including DCIS and results in elevated concentrations of intratumoral estradiol. These findings could provide the scientific rationale as to employing aromatase inhibitors in the management of ER positive DCIS patients.
J Steroid Biochem Mol Biol 2010 Feb 28
PMID:Aromatase and in situ estrogen production in DCIS (ductal carcinoma in situ) of human breast. 1978 35

Estrogen receptor (ER)alpha is a critical target of therapeutic strategies to control the proliferation of hormone-dependent breast cancers. Preferred clinical options have significant adverse side effects that can lead to treatment resistance due to the persistence of active estrogen receptors. We have established the cellular mechanism by which indole-3-carbinol (I3C), a promising anticancer phytochemical from Brassica vegetables, ablates ERalpha expression, and we have uncovered a critical role for the GATA3 transcription factor in this indole-regulated cascade. I3C-dependent activation of the aryl hydrocarbon receptor (AhR) initiates Rbx-1 E3 ligase-mediated ubiquitination and proteasomal degradation of ERalpha protein. I3C inhibits endogenous binding of ERalpha with the 3'-enhancer region of GATA3 and disrupts endogenous GATA3 interactions with the ERalpha promoter, leading to a loss of GATA3 and ERalpha expression. Ectopic expression of GATA3 has no effect on I3C-induced ERalpha protein degradation but does prevent I3C inhibition of ERalpha promoter activity, demonstrating the importance of GATA3 in this I3C-triggered cascade. Our preclinical results implicate I3C as a novel anticancer agent in human cancers that coexpress ERalpha, GATA3, and AhR, a combination found in a large percentage of breast cancers but not in other critical ERalpha target tissues essential to patient health.
Mol Biol Cell 2010 Apr 01
PMID:Indole-3-carbinol triggers aryl hydrocarbon receptor-dependent estrogen receptor (ER)alpha protein degradation in breast cancer cells disrupting an ERalpha-GATA3 transcriptional cross-regulatory loop. 2013 88

Estrogen receptor (ER) status is a strong predictor of response to hormonal therapy in women with breast cancer. Not only presence of ER, but also level of expression has been shown to correlate with time to recurrence in patients undergoing therapy with tamoxifen or anastrozole. In addition, risk reduction occurs in ER-negative, progesterone receptor (PR)-positive patients treated with hormonal therapy. Immunohistochemistry (IHC) has been the method of choice for determining hormone receptor status. Recently, Genomic Health began reporting ER and PR status measured quantitatively by reverse transcription-polymerase chain reaction (RT-PCR) as a component of its Oncotype DX assay. As part of our quality assurance program, we reviewed 80 breast cancer cases that had been evaluated by the Oncotype DX assay and also underwent immunohistochemical staining for ER and PR. We found excellent correlation between ER and PR status determined qualitatively by each method. In addition, when hormone receptor expression measured quantitatively by RT-PCR and semiquantitatively by IHC were compared, results showed linear correlation. Given the additional advantages of hormone receptor IHC performed on intact tissue sections, currently there is no definitive reason to switch to RT-PCR for determination of ER and PR expressions.
Appl Immunohistochem Mol Morphol 2010 May
PMID:Concordance between semiquantitative immunohistochemical assay and oncotype DX RT-PCR assay for estrogen and progesterone receptors. 2018 46

Estrogen receptor-related receptor alpha (ERRalpha) is an orphan member of the nuclear receptor superfamily of transcription factors. ERRalpha is highly expressed in the prostate, especially in prostate stromal cells. However, little is known about the regulation and function of ERRalpha, which may contribute to the progression of prostatic diseases. We previously found that prostaglandin E2 (PGE2) up-regulated the expression of aromatase in prostate stromal cells. Here we show that PGE2 also up-regulates the expression of ERRalpha, which, as a transcription factor, further mediates the regulatory effects of PGE2 on the expression of aromatase. ERRalpha expression was up-regulated by PGE2 in prostate stromal cell line WPMY-1, which was mediated mainly through the protein kinase A signaling pathway by PGE2 receptor EP2. Suppression of ERRalpha activity by chlordane (an antagonist of ERRalpha) or small interfering RNA knockdown of ERRalpha blocked the increase of expression and promoter activity of aromatase induced by PGE2. Overexpression of ERRalpha significantly increased aromatase expression and promoter activity, which were further augmented by PGE2. Chromatin immunoprecipitation assay demonstrated that ERRalpha directly bound to the aromatase promoter in vivo, and PGE2 enhanced the recruitment of ERRalpha and promoted transcriptional regulatory effects on aromatase expression in WPMY-1. 17Beta-estradiol concentration in WPMY-1 medium was up-regulated by ERRalpha expression, and that was further increased by PGE2. Our results provided evidence that ERRalpha contributed to local estrogen production by up-regulating aromatase expression in response to PGE2 and provided further insights into the potential role of ERRalpha in estrogen-related prostatic diseases.
Mol Endocrinol 2010 Jun
PMID:Estrogen receptor-related receptor alpha mediates up-regulation of aromatase expression by prostaglandin E2 in prostate stromal cells. 2035 Nov 96

Beta-amyloid peptide (betaAP) induces apoptosis and down-regulation of alpha(1)beta(1) integrin in neuronal cells, indicating a relationship between betaAP neurotoxicity and modulation of integrin expression. Estrogen may play a role in protecting women from Alzheimer Disease (AD). It is here reported that both 17beta-estradiol (17betaE(2)) and its non-estrogenic stereoisomer 17alpha-estradiol (17alphaE(2)) rescue neuronal cells from betaAP-induced apoptosis. As cellular model, the human neuroblastoma cell line SK-N-BE was used, which responds to retinoic acid by growth arrest and differentiation toward the neuronal phenotype (RA-SK-N-BE). Estrogen receptor antagonist does not hinder estrogen protection. Inhibition of phosphatidylinositol 3-kinase (PI3-K), but not of tyrosine kinases or mitogen-activated protein kinases (MAPK) blocks 17betaE(2) protection against betaAP-induced apoptosis. 17betaE(2) up-regulates alpha(1)beta(1) integrin expression and completely abolishes betaAP-induced alpha(1)beta(1) down-regulation. Inadequate cell cycle control may contribute to neuronal death in AD. betaAP induces RA-SK-N-BE cells to enter cell cycle, which remains incomplete. 17betaE(2) induces betaAP-treated cells to complete cell cycle. Our data suggest that estrogen protects from betaAP neurotoxicity by restoring integrin expression and cell cycle control.
Mol Cell Neurosci 2010 Oct
PMID:Estrogen and beta-amyloid toxicity: role of integrin and PI3-K. 2053 57


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