Background: Estrogen receptor (ER)-negative breast tumors and progesterone receptor (PR)-negative breast tumors occur more commonly in women of African ancestry. Recent research indicates that the effects of reproductive factors may differ by hormone receptor status. We assessed the relation of parity and lactation to incidence of ER−/PR− and ER+/PR+ breast cancer in a cohort of African American women.. Methods: From 1995-2009, 457 incident cases of ER+/PR+ and 318 cases of ER−/PR− breast cancer were confirmed by review of pathology data among 59,000 African American women followed in the Black Womens Health Study through biennial questionnaires. HRs and two-sided 95% CIs for the incidence of breast cancer subtypes were derived from proportional hazards regression models that controlled for age, reproductive variables, and breast cancer risk factors.. Results: Higher parity was associated with an increased risk of ER−/PR− breast cancer (HR = 1.48, 95% CI: 0.98-1.84 for 3+ versus 0 ...
The ligand binding domain of estrogen receptor and estrogen receptor-related receptors. The ligand binding domain of estrogen receptor (ER) and estrogen receptor-related receptors (ERRs): Estrogen receptors are a group of receptors which are activated by the hormone estrogen. Estrogen regulates many physiological processes including reproduction, bone integrity, cardiovascular health, and behavior. The main mechanism of action of the estrogen receptor is as a transcription factor by binding to the estrogen response element of target genes upon activation by estrogen and then recruiting coactivator proteins which are responsible for the transcription of target genes. Additionally some ERs may associate with other membrane proteins and can be rapidly activated by exposure of cells to estrogen. ERRs are closely related to the estrogen receptor (ER) family. But, it lacks the ability to bind estrogen. ERRs can interfere with the classic ER-mediated estrogen signaling pathway, positively or ...
In breast cancer, the presence of the ERα is considered as a good indicator of disease-free survival and prognosis since patients with ERα-positive tumors are candidates for hormonal therapy [3, 4, 6]. In contrast, tumors lacking this receptor have the poorest clinical prognosis [36]. In this study we demonstrated the ability of calcitriol to induce the expression of ERα in both primary and established ERα-negative breast cancer cell lines. This effect was mediated by a VDR-dependent mechanism. In addition, our results demonstrated a fully active calcitriol-induced ER by its ability to increase PRL gene expression. Interestingly, pretreatment of ER-negative breast tumor-derived cells with calcitriol and the further incubation with this secosteroid in combination with tamoxifen or ICI-182,780 resulted in a significantly lower cell growth proliferation.. It is noteworthy to mention that, to our knowledge, this study is the first to demonstrate the ability of calcitriol to induce the expression ...
Pregnancy is safe for women with estrogen receptor positive breast cancerSome people have basic questions about how pregnancy happens. Some may have questions about avoiding a pregnancy
A striking difference between ER+ and ER- disease is emerging at the level of mRNA expression. Although in ER+ disease a significant number of genes have been found that correlate with clinical outcome [5, 10, 18, 22], in ER- disease no such prognostic signatures have thus far been reported. Moreover, although in ER+ tumors subtypes of different prognostic risks, the luminal A and B subtypes, have been defined [21, 22], no such subdivisions have been noted for ER- breast cancer. It is known that the two main subtypes of ER- breast cancer (ER-/HER2+ and basals) have worse prognosis compared with the luminal A subtype, but no outcome differences between the ER-/HER2+ and basal subtypes have been observed [15, 21-23, 26].. We believe that these differences between ER+ and ER- disease are related to the different histopathologic characteristics of the tumors. The prognostic signatures derived for ER+ breast cancer are characterized by genes related to cell cycle and cell proliferation pathways, and ...
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The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer and stop it from growing. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body ...
The study is being conducted to determine whether neoadjuvant endocrine therapy with fulvestrant or the combination of anastrozole and fulvestrant, is better than anastrozole when given before surgery to shrink the cancer and stop it from growing. Anastrozole inhibits tumor growth by reducing the levels of estrogen and has been approved by the Food and Drug Administration (FDA) of the United States for use after surgery for postmenopausal women with estrogen receptor positive breast cancer. It is also considered a standard of care to give anastrozole for a few months before surgery to shrink the tumor. Fulvestrant inhibits tumor cell growth by reducing the levels of estrogen receptor in the tumor cell. It is not approved by the FDA for use in women with early stage breast cancer before or after surgery, but is approved by the FDA for patients with advanced (Stage 4) estrogen receptor positive breast cancer that has spread to other parts of the body ...
Women are believed to be protected from non-alcoholic fatty liver disease (NAFLD) by estrogen, so postmenopausal women with lower estrogen levels have an increased chance of developing the disease. Their risk is even higher if they are on anti-estrogen therapy. Hepatic steatosis (fatty liver) is is an early stage of NAFLD which can lead to […]. View Post ...
Currently, after surgery, chemotherapy or radiation, hormonal therapy is used as an adjuvant treatment to help reduce the risk of cancer recurrence. These CYP3A4 inhibitors could be used in conjunction with hormonal therapy to help decrease the risk of cancer recurrence, or to slow down the progress of metastatic cancer. At low doses, these inhibitors were found to activate AMPK and to be more potent than Metformin, indicating they could be an effective treatment for type 2 diabetes and to promote weight loss in obese patients. BENEFITS AND FEATURES OF CYP3A4 INHIBITORS:. ...
TY - JOUR. T1 - Expression of estrogen receptor gene in mouse oocyte and during embryogenesis. AU - Wu, T. C J. AU - Wang, L.. AU - Wan, Yu-Jui Yvonne. PY - 1992. Y1 - 1992. N2 - Estrogen is required for oocyte maturation and embryonic development in vivo; however, the mechanism involved is not clear. Since the effect of estrogen is mediated through the estrogen receptor (ER), we examined the ontogeny and expression of the ER gene in mouse oocytes and embryos of various gestational stages using the highly sensitive reverse transcriptase- polymerase chain reaction (RT-PCR) technique. Total RNA, extracted from 40 ovulated oocytes, 2-cell embryos, morulae, and blastocysts, was reverse transcribed into cDNA. A pair of primers flanking the 453-bp region encoding the hormone-binding domain of ER was used for 30 cycles of PCR. The identity of the amplified product was confirmed by sizing and Southern blot hybridization. The results indicated that ER gene is expressed in unfertilized oocytes and ...
Estrogen receptor-negative (ER(-)) breast cancers have limited treatment options and are associated with earlier relapses. Because glucocorticoid receptor (GR) signaling initiates antiapoptotic pathways in ER(-) breast cancer cells, we hypothesized that activation of these pathways might be associated with poor prognosis in ER(-) disease. Here we report findings from a genome-wide study of GR transcriptional targets in a premalignant ER(-) cell line model of early breast cancer (MCF10A-Myc) and in primary early-stage ER(-) human tumors. Chromatin immunoprecipitation with massively parallel sequencing (ChIP-seq) coupled to time-course expression profiling led us to identify epithelial-to-mesenchymal transition (EMT) pathways as an important aspect associated with GR activation. We validated these findings by carrying out a meta-analysis of primary breast tumor gene expression from 1,378 early-stage breast cancer patients with long-term clinical follow-up, confirming that high levels of GR expression
Summary Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Introduction Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip ...
Estrogen receptors (ERs), including ERα and ERβ, mainly mediate the genotype effect of estrogen. ERα is highly expressed in most breast cancers. Endocrine therapy is the most effective and safety adjunctive therapy for ER positive breast cancers. RNPC1, an RNA binding protein (RBP), post-transcriptionally regulating gene expression, is emerging as a critical mechanism for gene regulation in mammalian cells. In this study, we revealed RNPC1s capability of regulating ERα expression. There was a significant correlation between RNPC1 and ERα expression in breast cancer tissues. Ectopic expression of RNPC1 could increase ERa transcript and expression in breast cancer cells, and vice versa. Consistent with this, RNPC1 was able to bind to ERα transcript to increase its stability. Furthermore, overexpression of ERα could decrease the level of RNPC1 transcript and protein. It suggested a novel mechanism by which ERα expression was regulated via stabilizing mRNA. A regulatory feedback loop ...
Analysis of lipid components of membranes in breast cancer cells was done previously and revealed significantly altered ratio of phospholipids (3), increased level of gangliosides, and components of lipid rafts (4-6) in ER(−) cells. Furthermore, increased circulating levels of gangliosides were found in breast cancer patients when compared with healthy individuals (7). Although association of few membrane and cytoskeletal proteins with the ER status were reported before, no comprehensive analysis of membrane and cytoskeletal proteins in a broad cell panel of breast cancer cells has been done thus far. Among these proteins, vimentin, EGFR, CD44, fascin, and E-cadherin were shown to be highly correlated with ER status both in breast cancer cell lines and in clinical samples (17). EGFR and vimentin were shown to coexpress in specific subset of advanced breast carcinoma distinct from both erbB2(+) and ER(+) cases (17). CD44, moesin, and fascin were also found to express at higher level in advanced ...
While ER- breast cancer risk was markedly reduced in women with a late age at menarche, there was not a clear pattern of increased risk with longer interval between menarche and FLB, as was observed for ER+ breast cancer. These findings indicate that etiologic pathways involving adolescence and preg …
Objective: Breast carcinomas positive for the estrogen receptor (ER+) but negative for the progesterone receptor (PR-) have unfavorable prognostic features and are resistant to tamoxifen therapy. The goal of this study was to highlight the significance of PR-breast carcinomas. ...
New and emerging treatments for estrogen receptor-positive breast cancer: focus on everolimus Elisavet Paplomata, Ruth O’ReganDepartment of Hematology and Medical Oncology, Winship Institute of Emory University, Atlanta, GA, USAAbstract: Management of patients with metastatic hormone receptor-positive breast cancer poses a challenge due to the inevitable development of endocrine resistance. Hormone resistance is associated with a complex interaction of the estrogen receptor with growth factors, transmembrane receptors, and intracellular growth cascades. The PI3K/Akt/mTOR pathway plays a major role in hormone resistance and proliferation of breast cancer. Preclinical and clinical data indicate that inhibitors of human epidermal growth factor receptor-2, epidermal growth factor receptor, insulin-like growth factor-1 receptor, and the mammalian target of rapamycin pathway may act synergistically with hormone therapy to circumvent endocrine resistance. Everolimus is currently approved for combination
Li, J., Gong, Y., Shen, P., Wong, S.P., Yong, E.L., Lee, L., Wise, S.D. (2009). Bioassays for estrogenic activity: Development and validation of estrogen receptor (ERα/ERβ) and breast cancer proliferation bioassays to measure serum estrogenic activity in clinical studies. Assay and Drug Development Technologies 7 (1) : 80-89. [email protected] Repository. https://doi.org/10.1089/adt. ...
Background: Drugs targeting estrogen signaling or production have become useful in preventing estrogen receptor‐positive breast cancers, but not estrogen receptor‐negative (ER‐negative) breast cancers. Our laboratory has demonstrated that rexinoids prevent ER‐negative mammary tumors in transgenic mice by 90%. However, since these agents are not 100% effective, we are investigating the mechanism by which rexinoids prevent cancer to develop more efficacious prevention strategies. We hypothesized that by identifying molecules regulated by the rexinoid LG100268, future chemopreventive agents could be developed to target these molecules alone or in combination with rexinoids to totally prevent breast cancer development. To investigate this hypothesis we utilized an Affymetrix genome array to identify biomarkers regulated by LG100268.. Methods: Cell counts were used to confirm rexinoid‐induced growth suppression in normal human mammary epithelial cells (HMECs). TUNEL analysis was conducted ...
9q31.2-rs865686 as a susceptibility locus for estrogen receptor-positive breast cancer: evidence from the breast cancer association consortium ...
Purpose: The 21-gene breast cancer assay recurrence score (RS) is widely used for assessing recurrence risk and predicting chemotherapy benefit in patients with estrogen receptor (ER) -positive breast cancer. Pathologic and clinical factors such as tumor size, grade, and patient age also provide independent prognostic utility. We developed a formal integration of these measures and evaluated its prognostic and predictive value. Patients and Methods: From the National Surgical Adjuvant Breast and Bowel (NSABP) B-14 and translational research cohort of the Arimidex, Tamoxifen Alone or in Combination (TransATAC) studies, we included patients who received hormonal monotherapy, had ER-positive tumors, and RS and traditional clinicopathologic factors assessed (647 and 1,088, respectively). Individual patient risk assessments from separate Cox models were combined using meta-analysis to form an RS-pathology-clinical (RSPC) assessment of distant recurrence risk. Risk assessments by RS and RSPC were ...
A hormone-receptor-positive (HR+) tumor is a tumor which consists of cells that express receptors for certain hormones. The term most commonly refers to estrogen receptor positive tumors (i.e. tumors that contain estrogen receptor positive cells), but can also include progesterone receptor positive tumors. Estrogen-receptor-positive tumors depend on the presence of estrogen for ongoing proliferation. ...
TY - JOUR. T1 - Estrogen response elements function as allosteric modulators of estrogen receptor conformation. AU - Wood, Jennifer R.. AU - Greene, Geoffrey L.. AU - Nardulli, Ann M.. PY - 1998/4. Y1 - 1998/4. N2 - The estrogen receptor (ER) is a ligand-dependent transcription factor that regulates the expression of estrogen-responsive genes. ER-mediated transcriptional changes are brought about by interaction of the ER with the estrogen response element (ERE). In this study, we examined the interaction of the Xenopus laevis ER DNA binding domain (DBD) and the intact ER with the X. laevis vitellogenin A2 ERE and the human pS2 ERE. Using gel mobility shift, DNase I footprinting, and methylation interference assays, we demonstrated that the DBD bound only as a dimer to the A2 ERE. However, the DBD bound as a monomer to the consensus pS2 ERE half site at lower DBD concentrations and then as a homodimer to the consensus and imperfect pS2 ERE half site at higher DBD concentrations. Antibody ...
Estrogen receptor (ER) has been shown to be involved in several cellular and metabolic pathways. In this study, we reviewed the literature for molecular and physiological roles of estrogen receptor in normal and pathological conditions. We discussed the expression of estrogen receptor in several tissues as well as the potential of using ERb agonists in treating proliferative hematological disorders. The function of estrogen is varied and may look contradicted. Estrogen has multiple roles under physiological conditions including signaling roles in cell growth, reproduction, development and differentiation. Estrogens exert their effects through two distinct estrogen receptors, ER-α and β to which E2 binds strongly. The expression of ERs depends mainly on the type of ER. Although estrogen mainly acts in reproductive system, its receptors are selectively expressed in different tissues. ER-β is highly expressed in the ovary, central nervous system, cardiovascular system, lung, male reproductive
A small number of single biomarkers has been used for several years in various aspects of managing breast cancer, including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Their study in new settings and/or alongside new therapies has extended their applications. The biological importance of these established markers has been reinforced over the last decade by the results from genomic classification in which the presence or absence of these markers identifies the three main groups (7): luminal (estrogen receptor positive), HER2-like (mainly estrogen receptor negative and HER2 positive), and basal-like (mainly estrogen receptor negative, progesterone receptor negative, and HER2 negative), which approximates the so-called triple-negative group of breast cancer as described by Schneider et al. in this issue (8). The development of such different molecular groups according to estrogen receptor status may be determined at least partly by the apparent ...
The role of estrogen receptor β (ERβ) in breast cancer is still under investigation. Various studies have provided evidence that ERβ behaves as a tumor suppressor in breast cancer, whereas some studies of estrogen receptor α (ERα) negative breast cancer reported a positive correlation between high ERβ expression and poor prognostic phenotypes, such as induced proliferation, invasion and metastasis. In the present immunohistochemistry study of 99 ERα/progesterone receptor (PR)-negative breast cancer samples, nuclear expression of ERβ was positively associated with membranous expression of breast cancer resistance protein (BCRP), Ki67 (proliferation marker) and tumor size. Moreover, both endogenous and exogenous ERβ upregulated BCRP expression which induced BCRP-mediated drug resistance and enhanced proliferation of ERα-/PR- breast cancer cells in the presence of 17β-estradiol, whereas these effects were reversed by additional use of tamoxifen (TAM). In addition, the regulation of BCRP ...
Estrogens play a central role in the development of breast cancer. Most breast carcinomas are detected after menopause and despite a low degree of ovarian estrogen production and low levels of serum estrogen these tumors show a high in situ level of estrogens. Enzymes modulating local steroid availability seem to play an important role in the progression of especially estrogen receptor positive breast cancer. The 17ß-hydroxysteroid dehydrogenase (17ß-HSD) enzymes are involved in the interconversion of biologically active and inactive sex steroids and are considered to play a critical role in the in situ metabolism of estrogen.. The aim of this thesis was to investigate the expression of 17ß-HSD type 1 and 2 in breast cancer and correlate this to prognosis, and to analyze if the gene encoding 17ßHSD type 1 exhibits altered gene copy number in breast cancer. We also wanted to examine if the protein levels of aromatase, 17ßHSD type 1 and 17ßHSD type 2 show association with the expression of ...
TY - JOUR. T1 - Novel estrogen receptor ligands based on an anthranylaldoxime structure. T2 - Role of the phenol-type pseudocycle in the binding process. AU - Minutolo, Filippo. AU - Antonello, Michela. AU - Bertini, Simone. AU - Ortore, Gabriella. AU - Placanica, Giorgio. AU - Rapposelli, Simona. AU - Sheng, Shubin. AU - Carlson, Kathryn E.. AU - Katzenellenbogen, Benita S. AU - Katzenellenbogen, John A.. AU - Macchia, Marco. PY - 2003/9/11. Y1 - 2003/9/11. N2 - The 3,4-diphenylsalicylaldoxime system 1 is an estrogen receptor (ER) ligand of unusual structure, having a hydrogen-bonded pseudocyclic A′-ring in place of the paradigmatic phenolic A-ring that is characteristic of most estrogens. We have investigated the role played by the pseudocycle A′ in binding to the ER by preparing 3,4-diphenylbenzaldoxime (4), a compound that completely lacks this ring but still preserves all of the other features of the original molecule 1, as well as a series of 3,4-diphenylanthranylaldoximes (5a-c) in ...
This report provides the insights of the marketed drugs for the Estrogen Receptor Positive (ER+) Breast Cancer which includes the Targeted Therapy, Hormone Therapy and Chemotherapy. In case of Estrogen Receptor Positive (ER+) Breast Cancer, Hormone therapy is the main focus of treatment after surgery and chemotherapy. Hormonal therapy is usually recommended after 5 years of surgery and can be divided into Estrogen blocking hormonal therapy and estrogen lowering hormonal therapy based on the mechanism of action of the hormonal therapy drugs. Of all the late-stage pipeline drugs, Buparlisib is expected to reach the market in the next few years ...
TY - JOUR. T1 - Synthesis and estrogen receptor affinity of a 4-hydroxytamoxifen-labeled ligand for diagnostic imaging. AU - Lashley, Matthew R.. AU - Niedzinski, Edmund J.. AU - Rogers, Jane M.. AU - Denison, Michael S.. AU - Nantz, Michael H.. PY - 2002/12/1. Y1 - 2002/12/1. N2 - A 10-step synthesis of a novel 4-hydroxytamoxifen-DTPA ligand (HOTam-DTPA) is reported. Tamoxifen and its primary metabolite 4-hydroxytamoxifen are common estrogen receptor ligands. Consequently, tamoxifen has found utility as the targeting component of various diagnostic agents for selective imaging of estrogen receptor-rich tissue, specifically breast cancer. An L-aspartic acid-derived DTPA analogue was attached to the ethyl side chain of 4-hydroxy-tamoxifen using N,N′-dimethylethylenediamine as a hydrophilic linker. A competitve estrogen receptor binding assay using [3H]-17β-estradiol was performed to determine the effect of the ethyl side chain modification on estrogen receptor affinity. The results show that ...
HypothesisSome risk factors associated with breast cancer may be more predictive of estrogen receptor (ER)− positive than ER-negative tumors.DesignSurvey of pat
Investigators from the Slone Epidemiology Center at Boston University School of Medicine (BUSM) have reported that African American women who consume more vegetables are less likely to develop estrogen receptor-negative breast cancer than women with low vegetable intake. The study results, published in the American Journal of Epidemiology, were based on data from the Black Womens Health Study (BWHS), a large follow-up study of 59,000 African American women from across the U.S. conducted by investigators at the Slone Epidemiology Center since 1995.. The investigators followed 51,928 participants in the BWHS for 12 years, during which time 1,268 cases of breast cancer developed. Among cases on which hormone receptor status was obtained, 35 percent were estrogen receptor-negative/progesterone receptor-negative (ER-/PR-) breast cancers. The incidence of ER-/PR- breast cancer was 43 percent lower among women consuming at least two vegetables per day compared with women who ate fewer than four ...
Fulvestrant is a synthetic estrogen receptor antagonist. Unlike tamoxifen (which has partial agonist effects) and the aromatase inhibitors (which reduce the estrogen available to tumor cells), fulvestrant binds competitively to estrogen receptors in breast cancer cells, resulting in estrogen receptor deformation and decreased estrogen binding. In vitro studies indicate that fulvestrant reversibly inhibits the growth of tamoxifen-resistant, estrogen-sensitive, human breast cancer cell lines. Check for active clinical trials or closed clinical trials using this agent.
who showed paclitaxel once per week comparedwith paclitaxel once every 3 weeks increased pathologic completeresponse-a surrogate of disease-free and overall survival-inthe neoadjuvant setting in operable breast cancer, in both hormonereceptor-positiveandhormonereceptor-negative subsets. In the confirmatorytrial by Sparano et al,2 which evaluated the 5-year diseasefreeand overall survival end points and compared the two taxanesand the two taxane schedules in a 2 x 2 factorial design, paclitaxelonce per week compared with paclitaxel once every 3 weeks significantlyimproved 5-year progression-free survival in hormonereceptor-negative breast cancer, including triple-negative and humanepidermal growth factor receptor 2 (HER2) -positive subsets ofbreast cancer, and hormone receptor-positive breast cancer, whichcombines luminal-A and luminal-B subtypes of breast cancer. Thiswas seen despite the fact that patients with HER2-positive breastcancer (including luminal-B breast cancer, an HER2-positive ...
A small number of single biomarkers has been used for several years in various aspects of managing breast cancer, including estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2). Their study in new settings and/or alongside new therapies has extended their applications. The biological importance of these established markers has been reinforced over the last decade by the results from genomic classification in which the presence or absence of these markers identifies the three main groups (7): luminal (estrogen receptor positive), HER2-like (mainly estrogen receptor negative and HER2 positive), and basal-like (mainly estrogen receptor negative, progesterone receptor negative, and HER2 negative), which approximates the so-called triple-negative group of breast cancer as described by Schneider et al. in this issue (8). The development of such different molecular groups according to estrogen receptor status may be determined at least partly by the apparent ...
Dr. Sharon Glynn is Lecturer Above the Bar in Pathology at NUI Galway. She graduated in 1997 with a BSc in Biotechnology (Dublin City University) and in 2003 with a PhD entitled An investigation of the role of the ErbB receptor family in chemotherapeutic drug resistance and invasion in human breast cancer (Dublin City University). After graduation Dr. Glynn served as a research officer at the National Institute for Cellular Biotechnology in Dublin City University where she studied the efficacy of new therapeutics including cholesterol lowering statins on breast cancer and melanoma proliferation and invasion. From 2005 to 2009 Dr. Glynn worked as an NCI Cancer Prevention Fellow in Bethesda Maryland, USA in the Laboratory of Human Carcinogenesis under the mentorship of Dr. Stefan Ambs, studying the role of inflammation pathways in estrogen receptor negative breast cancer progression using an approach combining molecular epidemiology and basic laboratory science. She discovered a novel role for ...
The primary objective of this study is to determine whether overall response to cetuximab combined with cisplatin is better than overall response to cis
Vega V.B., Lin C.-Y., Lai K.S., Kong S.L., Xie M., Su X., Teh H.F., Thomsen J.S., Yeo A.L., Sung W.K., Bourque G., Liu E.T. (2006). Multiplatform genome-wide identification and modeling of functional human estrogen receptor binding sites. Genome Biology 7 (9) : R82. [email protected] Repository. https://doi.org/10.1186/gb-2006-7-9- ...
Tamoxifen - used alongside traditional chemotherapy and radiotherapy - blocks the female hormone oestrogen that, in certain breast cancers, is required by the tumour to grow; it has been shown to improve cancer survival rates by up to one third.. However, about one third of patients with the appropriate type of breast cancer - known as oestrogen receptor positive breast cancer - do not respond to tamoxifen or develop resistance to the drug. Oestrogen receptor positive breast cancer is the most common form of the disease accounting for 70% of cases.. Now, a team from the University of Manchesters Paterson Institute for Cancer Research has identified a molecular flag that will help doctors predict which patients will respond best to complementary (adjuvant) hormone therapy with tamoxifen.. The identification of molecular flags to classify subgroups of breast cancer and so determine the best treatment for each patient is of increasing importance in cancer therapy, said study lead Professor ...
TY - JOUR. T1 - Proteasome-dependent degradation of the human estrogen receptor. AU - Nawaz, Zafar. AU - Lonard, David M.. AU - Dennis, Andrew P.. AU - Smith, Carolyn L.. AU - OMalley, Bert W.. PY - 1999/3/2. Y1 - 1999/3/2. N2 - In eukaryotic cells, the ubiquitin-proteasome pathway is the major mechanism for the targeted degradation of proteins with short half-lives. The covalent attachment of ubiquitin to lysine residues of targeted proteins is a signal for the recognition and rapid degradation by the proteasome, a large multi-subunit protease. In this report, we demonstrate that the human estrogen receptor (ER) protein is rapidly degraded in mammalian cells in an estradiol-dependent manner. The treatment of mammalian cells with the proteasome inhibitor MG132 inhibits activity of the proteasome and blocks ER degradation, suggesting that ER protein is turned over through the ubiquitin- proteasome pathway. In addition, we show that in vitro ER degradation depends on ubiquitin-activating E1 ...
In approximately two-thirds of cases, ER-positive breast cancer is characterized by the sustained expression of the ER-α (ESR1), making this receptor the most frequently utilized biomarker and therapeutic target for ER-positive disease.. Genetic mutations fuelling ESR1 expression in ER-positive breast cancer have been studied extensively, therefore, in this study the team aimed to look beyond genetic mutations. Utilizing epigenetics, the team observed a significant number of somatic mutations in a set of regulatory elements that have previously been demonstrated to regulate ESR1 expression in 7% of ER-positive breast cancers.. Lead author Mathieu Lupien (Princess Margaret Cancer Centre) commented: By investigating acquired mutations found outside of genes through the power of epigenetics, we have identified that functional regulatory components can be altered to impact the expression of genes to promote breast cancer development.. Lupien believes that this research highlights the importance ...
Deca-bromodiphenyl ether (BDE-209) regulates various aspects of spermatogenesis and male fertility through its effect on estrogen receptor α (ERα
GPER/GPR30 is a seven-transmembrane G protein-coupled estrogen receptor that regulates many aspects of mammalian biology and physiology. We have previously described both a GPER-selective agonist G-1 and antagonist G15 based on a tetrahydro-3H-cyclopenta[c]quinoline scaffold. The antagonist lacks an ethanone moiety that likely forms important hydrogen bonds involved in receptor activation. Computational docking studies suggested that the lack of the ethanone substituent in G15 could minimize key steric conflicts, present in G-1, that limit binding within the ER? ligand binding pocket. In this report, we identify low-affinity cross-reactivity of the GPER antagonist G15 to the classical estrogen receptor ER?. To generate an antagonist with enhanced selectivity, we therefore synthesized an isosteric G-1 derivative, G36, containing an isopropyl moiety in place of the ethanone moiety. We demonstrate that G36 shows decreased binding and activation of ER?, while maintaining its antagonist profile ...
In vertebrates, estrogens and estrogen mimicking chemicals modulate gene expression mainly through a genomic pathway mediated by the estrogen receptors (ERs). Although the existence of an ER orthologue in the mollusc genome has been known for some time, its role in estrogen signalling has yet to be deciphered. This is largely due to its constitutive (ligand-independent) activation and a limited mechanistic understanding of its regulation. To fill this knowledge gap, we cloned and characterised an ER cDNA (sgER) and the 5′-flanking region of the gene from the Sydney rock oyster Saccostrea glomerata. The sgER cDNA is predicted to encode a 477-amino acid protein that contains a DNA-binding domain (DBD) and a ligand-binding domain (LBD) typically conserved among both vertebrate and invertebrate ERs. A comparison of the sgER LBD sequence with those of other ligand-dependent ERs revealed that the sgER LBD is variable at several conserved residues known to be critical for ligand binding and receptor
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TY - JOUR. T1 - Abnormal vascular function and hypertension in mice deficient in estrogen receptor β. AU - Zhu, Yan. AU - Bian, Zhao. AU - Lu, Ping. AU - Karas, Richard H.. AU - Bao, Lin. AU - Cox, Daniel. AU - Hodgin, Jeffrey. AU - Shaul, Philip W.. AU - Thorén, Peter. AU - Smithies, Oliver. AU - Gustafsson, Jan Åke. AU - Mendelsohn, Michael E.. PY - 2002/1/18. Y1 - 2002/1/18. N2 - Blood vessels express estrogen receptors, but their role in cardiovascular physiology is not well understood. We show that vascular smooth muscle cells and blood vessels from estrogen receptor β (ERβ) - deficient mice exhibit multiple functional abnormalities. In wild-type mouse blood vessels, estrogen attenuates vasoconstriction by an ERβ-mediated increase in inducible nitric oxide synthase expression. In contrast, estrogen augments vasoconstriction in blood vessels from ERβ-deficient mice. Vascular smooth muscle cells isolated from ERβ-deficient mice show multiple abnormalities of ion channel function. ...
TY - JOUR. T1 - Estrogen receptor β protects against in vivo injury in RPE cells. AU - Elliot, Sharon J.. AU - Catanuto, Paola. AU - Espinosa-Heidmann, Diego G.. AU - Fernandez, Pedro. AU - Hernandez, Eleut. AU - Saloupis, Peter. AU - Korach, Kenneth. AU - Karl, Michael. AU - Cousins, Scott W.. N1 - Funding Information: This work was supported in part by National Institutes of Health, National Eye Institute Grant RO1 EY1447-04 (SJE, MK, and SWC). PY - 2010/1. Y1 - 2010/1. N2 - Epidemiological data suggest that estrogen deficiency in postmenopausal women may contribute to the severity of AMD. We discovered that 17β-estradiol (E2) was a crucial regulator of the severity of extracellular matrix turnover (ECM) dysregulation both in vivo and in vitro. We also found in vitro that the presence of estrogen receptor (ER)β regulates MMP-2 activity. Therefore in an attempt to delineate the role of the ER subtypes, female estrogen receptor knockout (ERKO) mice were fed a high-fat diet, and the eyes were ...
Discovery of LSZ102, a Potent, Orally Bioavailable Selective Estrogen Receptor Degrader (SERD) for the Treatment of Estrogen Receptor Positive Breast Cancer. Abstract: The estrogen receptor (ER) is a nuclear hormone receptor that regulates a variety of genes which promote both cell proliferation and cell cycle progression. In the clinical setting ER positive breast cancer accounts for approximately 2/3 of all breast cancer diagnoses. Anti-estrogen therapies, such as selective estrogen receptor modulators (SERMs) and aromatase inhibitors (AI), are the core treatment modalities in patients with ER positive breast cancer. Although a large proportion of patients respond positive to endocrine therapy, resistance to these drug treatments remains an impediment to durable clinical response. Selective estrogen receptor degraders (SERDs) that remove the receptor have been shown to be effective in this setting. We describe the discovery of LSZ102, a potent, orally available SERD found to inhibit ER ...
One-hundred and seventy patients with estrogen receptor positive (≥10 pmol/g protein) advanced breast cancer have been treated in a prospective randomized study either with continuous tamoxifen 30 mg × 1 daily (TAM), or with TAM 30 mg × 1 daily for 8 weeks alternating with medroxyprogesterone acetate 500 mg × 2 daily for 8 weeks (TAM/HD-MPA). The response rate was 62% in the group treated with cyclic TAM/HD-MPA versus 41% in the TAM alone group (p = 0.02). There was no significant difference in duration of remissions or survival.
Introduction- Estrogen-related receptor gamma (ERRγ) is an orphan nuclear receptor that has biological roles mainly in metabolism and it controls metabolic switching in perinatal heart. In adult heart diseases, however, the functional roles of ERRγ have not yet been elucidated.. Hypothesis- In the present study, we aimed to characterize the role of ERRγ in cardiac hypertrophy. Here we show that ERRγ provokes cardiac hypertrophy by inducing GATA4 and that its inverse agonist, GSK-5182, prevents cardiac hypertrophy.. Methods and Results- The functional roles of ERRγ in association with development of cardiac hypertrophy were examined in primarily cultured cardiomyocytes, in animal models, and in heart samples from human hypertrophic cardiomyopathy patients. ERRγ expression was increased in hearts obtained from human hypertrophic cardiomyopathy patients and in both agonist-induced cellular models and aortic banding-induced animal models of cardiac hypertrophy. Transgenic overexpression in ...
Despite progress in the management of breast cancer, the molecular underpinnings of clinically aggressive subtypes of the disease are not well-understood. Here, we show that activation of Notch developmental signaling in estrogen receptor (ER)-negative breast cancer cells results in direct transcriptional up-regulation of the apoptosis inhibitor and cell cycle regulator survivin. This response is associated with increased expression of survivin at mitosis, enhanced cell proliferation, and heightened viability at cell division. Conversely, targeting Notch signaling with a peptidyl gamma-secretase inhibitor suppressed survivin levels, induced apoptosis, abolished colony formation in soft agar, and inhibited localized and metastatic tumor growth in mice, without organ or systemic toxicity. In contrast, ER+ breast cancer cells, or various normal cell types, were insensitive to Notch stimulation. Therefore, ER- breast cancer cells become dependent on Notch-survivin signaling for their maintenance, in vivo.
Triple Negative Breasts Cancer tumor (TNBC) is a heterogeneous disease that predicated on immunohistochemistry (IHC) is estrogen receptor (ER) detrimental, progesterone receptor (PR) detrimental and individual epidermal growth aspect receptor 2 (HER2) detrimental. Triple Negative Breasts Cancer (TNBC) is normally a subtype of breasts cancer that predicated on immunohistochemistry (IHC) is normally estrogens receptor (ER) detrimental, progesterone receptor (PR) detrimental and individual epidermal growth aspect receptor 2 (HER2) detrimental [1]. TNBC is normally seen as a its exclusive molecular profile, intense nature, distinctive metastatic patterns and insufficient targeted therapies. Its estimated that from the world-wide breast cancer tumor burden, around 170,000 situations are TNBC and take into account ~10-20% of intrusive breast malignancies [1,2]. Molecular Profile and IHC Phenotype Breasts cancers are usually categorized into seven subtypes (3): luminal A (ER positive and histologic ...
The Ets-1 transcription factor is a candidate breast cancer oncogene that regulates the expression of genes involved in tumor progression and metastasis. Ets-1 signaling has also been linked to the development of a basal-like breast cancer phenotype. We recently described a nitric oxide (NO)-induced gene signature that is associated with poor disease outcome in estrogen receptor-negative (ER-) breast cancer and contains both stem cell-like and basal-like components. Thus, we examined the role of Ets-1 in NO signaling and NO-induced phenotypes in ER- human breast cancer cells. Promoter region analyses were performed on genes upregulated in inducible nitric oxide synthase (NOS2) high expressing tumors for Ets-binding sites. In vitro mechanisms were examined in human basal-like breast cancer cells lines. NO signaling effects were studied using either forced NOS2 expression or the use of a chemical NO-donor, diethlylenetriamine NONOate (DETANO). Promoter region analysis of genes that are up-regulated in
Estrogen receptor negative (ER(−)) breast cancer is aggressive, responds poorly to current treatments and has a poor prognosis. The NF-κB signaling pathway is implicated in ER(−) tumorigenesis. Aspirin (ASA) is chemopreventive against ER(+) but not for ER(−) breast cancers. Nitric oxide-releasing aspirin (NO-ASA) is a safer ASA where ASA is linked to an NO-releasing moiety through a spacer. In vitro, we investigated anti-proliferation effects of NO-ASA (para- and meta-isomers) against ER(−) breast cancer cells MDA-MB-231 and SK-BR-23, effects on NF-κB signaling, and reactive oxygen species by standard techniques. In vivo, effects of NO-ASA were evaluated in a mouse xenograft model using MDA-MB-231 cells. p-NO-ASA inhibited the growth of MDA-MB-231 and SK-BR-3 cells at 24 h, the respective IC50s were 13 ± 2 and 17 ± 2 μM; ASA had an IC50 of |3000 μM in both cell lines. The IC50s for m-NO-ASA in MDA-MB-231 and SK-BR-3 were 173 ± 15 and 185 ± 12 μM, respectively, therefore, implying p-NO
Title: GPER and ER: Estrogen Receptors with Distinct Biological Roles in Breast Cancer. VOLUME: 11 ISSUE: 4. Author(s):Edward J. Filardo. Affiliation:Rhode Island Hospital, Department of Medicine, 593 Eddy Street, Aldrich Building Rm 708, Providence, RI 02903, USA.. Keywords:Estrogen, G-protein-coupled estrogen receptor (GPER), seven transmembrane receptors, estrogen receptors (ERs), nuclear steroid hormone receptors, tamoxifen, faslodex, epidermal growth factor receptors (EGFRs), aromatase inhibitors, breast cancer. Abstract: Comparative clinical studies indicate that blockade of estrogen biosynthesis by the use of aromatase inhibitors may have benefit over estrogen receptor (ER) antagonism as a strategy for treating breast cancer. One plausible explanation for this idea is that more than one type of estrogen receptor may promote the biological effects of estrogen. Recent findings that G-protein-coupled receptor-30, (GPR30/GPER) promotes specific estrogen binding and manifests plasma ...
Common variants in 94 loci have been associated with breast cancer including 15 loci with genome-wide significant associations (P,5 x 10(-8)) with oestrogen receptor (ER)-negative breast cancer and BRCA1-associated breast cancer risk. In this study, to identify new ER-negative susceptibility loci, we performed a meta-analysis of 11 genome-wide association studies (GWAS) consisting of 4,939 ER-negative cases and 14,352 controls, combined with 7,333 ER-negative cases and 42,468 controls and 15,252 BRCA1 mutation carriers genotyped on the iCOGS array. We identify four previously unidentified loci including two loci at 13q22 near KLF5, a 2p23.2 locus near WDR43 and a 2q33 locus near PPIL3 that display genome-wide significant associations with ER-negative breast cancer. In addition, 19 known breast cancer risk loci have genome-wide significant associations and 40 had moderate associations (P,0.05) with ER-negative disease. Using functional and eQTL studies we implicate TRMT61B and WDR43 at 2p23.2 and ...
What is Triple Negative Breast Cancer? Triple negative breast cancer is not your normal form of breast cancer. It is often referred to as basal cell cancer because it does not express the three genes normally associated with breast cancer. These genes are estrogen receptor (ER), progesterone receptor (PR), or (HR)2.
TY - JOUR. T1 - Reliability of clinical estrogen receptor assays performed on tumor tissue biopsied from sites previously treated with radiotherapy. AU - Valenstein, Steven L.. AU - Voigt, Walter. AU - Vogel, Charles L.. AU - Thomsen, Sharon. AU - Sugarbaker, Everett V.. AU - Castro, Albert. AU - Gupta, Vicram. AU - Charyulu, Komanduri. PY - 1979/6. Y1 - 1979/6. N2 - The present retrospective analysis was done to determine whether previous radiotherapy to a biopsy site could be a source of false-negative estrogen receptor assays as suggested in earlier reports. The present study population included 56 women who had estrogen receptor assays done on tumor tissue obtained from skin, subcutaneous, or lymph node metastases. Tissue was taken from a previously irradiated area in 14 patients and from an unirradiated area in 42. Fifty-seven percent of the former and 50% of the latter patients had positive estrogen receptor assays, and quantitative levels of estrogen receptor also were comparable between ...
TY - JOUR. T1 - Triple negative breast cancer. T2 - A multi-omics network discovery strategy for candidate targets and driving pathways. AU - Karagoz, Kubra. AU - Sinha, Raghu. AU - Arga, Kazim Yalcin. PY - 2015/2/1. Y1 - 2015/2/1. N2 - Triple negative breast cancer (TNBC) represents approximately 15% of breast cancers and is characterized by lack of expression of both estrogen receptor (ER) and progesterone receptor (PR), together with absence of human epidermal growth factor 2 (HER2). TNBC has attracted considerable attention due to its aggressiveness such as large tumor size, high proliferation rate, and metastasis. The absence of clinically efficient molecular targets is of great concern in treatment of patients with TNBC. In light of the complexity of TNBC, we applied a systematic and integrative transcriptomics and interactomics approach utilizing transcriptional regulatory and protein-protein interaction networks to discover putative transcriptional control mechanisms of TNBC. To this ...
Clinical trial for Stage IB Breast Cancer | Estrogen Receptor-negative Breast Cancer | Stage II Breast Cancer | Triple Negative Breast Cancer | Progesterone Receptor-negative Breast Cancer | Stage IA Breast Cancer , MRI and Mammography Before Surgery in Patients With Stage I-II Breast Cancer
TY - JOUR. T1 - Body mass index, mammographic density, and breast cancer risk by estrogen receptor subtype. AU - Shieh, Yiwey. AU - Scott, Christopher G.. AU - Jensen, Matthew R.. AU - Norman, Aaron D.. AU - Bertrand, Kimberly A.. AU - Pankratz, V. Shane. AU - Brandt, Kathleen R. AU - Visscher, Daniel W. AU - Shepherd, John A.. AU - Tamimi, Rulla M.. AU - Vachon, Celine M. AU - Kerlikowske, Karla. PY - 2019/4/3. Y1 - 2019/4/3. N2 - Background: Obesity and elevated breast density are common risk factors for breast cancer, and their effects may vary by estrogen receptor (ER) subtype. However, their joint effects on ER subtype-specific risk are unknown. Understanding this relationship could enhance risk stratification for screening and prevention. Thus, we assessed the association between breast density and ER subtype according to body mass index (BMI) and menopausal status. Methods: We conducted a case-control study nested within two mammography screening cohorts, the Mayo Mammography Health Study ...
TY - JOUR. T1 - Repression of translation of human estrogen receptor α by G-quadruplex formation. AU - Balkwill, Graham D.. AU - Derecka, Kamila. AU - Garner, Thomas P.. AU - Hodgman, Charlie. AU - Flint, A. P F. AU - Searle, Mark S.. PY - 2009/12/8. Y1 - 2009/12/8. N2 - Tissue-specific expression of the human estrogen receptor α gene (ESR1) is achieved through multiple promoter sequences resulting in various mRNA transcripts encoding a common protein but differing in their 5′-untranslated region (5′-UTR). Many cancers are estrogen-sensitive with neoplastic growth stimulated through the estrogen receptor, a transcription factor that regulates developmental genes. We demonstrate that the human ESR1 gene is rich in potential quadruplex-forming sequences with 3 of 20 identified within exonic regions. In particular,we show using CD, UV, and NMR spectroscopy that a stable DNAG-quadruplex motif is formed within the exon C gene sequence. This motif, which PCR shows is transcribed in normal and ...
The final results are in-and they show that 500 mg of Faslodex® (fulvestrant) provides a significant advantage in overall survival compared to 250 mg of the drug in postmenopausal women with locally advanced or metastatic estrogen receptor-positive breast cancer recurring or progressing after prior endocrine therapy. The results were published online in the Journal of the National Cancer Institute.. Each year roughly 200,000 U.S. women are diagnosed with breast cancer. Many of these breast cancers will be hormone receptor-positive, meaning that they are stimulated to grow by the circulating female hormones estrogen and/or progesterone. Treatment of hormone receptor-positive breast cancer often involves hormonal therapies that suppress or block the action of estrogen.. Faslodex-a type of hormonal therapy known as an estrogen receptor antagonist-blocks the actions of estrogen. Its used for the treatment of metastatic, hormone receptor-positive breast cancer in postmenopausal women who experience ...
摘要Estrogen is well known to have a modulatory role on gastrointestinal tract, particularly through its interaction with nuclear estrogen receptors (ERs), alpha and beta (ERα/β). Recent functional studies also indicate that estrogen can activate a G-protein coupled estrogen receptor, GPR30, or GPER1. The present study was designed to identify either the presence or absence of nuclear ERs and GPR30 in the myenteric plexus of the stomach, duodenum, jejunum, ileum and colon of female and male mice. Immunofluorescence staining revealed a high expression of GPR30 in the cytoplasm but not within the nucleus of enteric neurons in female and male mice. ERβ localization was similar to GPR30, where it was expressed in cytoplasm of enteric neurons, but was absent from nuclei, opening up the possibility that ERβ and GPR30 might work together to manifest estrogenic effects. Comparatively, ERα was mainly located in the nuclei of enteric neurons. ERα, ERβ and GPR30 were also expressed in the ...
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Cheung CP, Yu S, Wong KB, Chan LW, Lai FM, Wang X, Suetsugi M, Chen S, Chan FL (Mar 2005). Expression and functional study of estrogen receptor-related receptors in human prostatic cells and tissues. The Journal of Clinical Endocrinology and Metabolism. 90 (3): 1830-44. doi:10.1210/jc.2004-1421. PMID 15598686 ...
In this follow-up study of African American women, oral contraceptive use was more strongly associated with an increased risk of ER−PR− breast cancer than of ER+PR+ breast cancer. The incidence of ER−PR− breast cancer increased significantly among recent users as the duration of use increased, with the largest increase (2.5-fold) among recent users whose duration of use was 10 or more years. However, there were some inconsistencies in that the incidence of ER−PR− cancer was also significantly increased for some shorter-duration and nonrecent categories of use. For ER+PR+ cancer, results were null for most categories of interval since last use and duration but there was a significant increase (1.66-fold) for recent users with 10 or more years of use. Results for ER+PR− tumors were null, but the numbers were small.. The present results strengthen the evidence that there is a stronger association of oral contraceptive use with ER− cancer than with ER+ cancer (32). In several ...
Triple-negative breast cancer (TNBC) is an aggressive clinical subtype of breast cancer that is characterized by the lack of estrogen receptor (ER) and progesterone receptor (PR) expression as well as human epidermal growth factor receptor 2 (HER2) overexpression. The TNBC subtype constitutes approximately 10%-20% of all breast cancers, but has no effective molecular targeted therapies. Previous meta-analysis of gene expression profiles of 587 TNBC cases from 21 studies demonstrated high expression of Wnt signaling pathway-associated genes in basal-like 2 and mesenchymal subtypes of TNBC. In this study, we investigated the potential of Wnt pathway inhibitors in effective treatment of TNBC. Activation of Wnt pathway was assessed in four TNBC cell lines (BT-549, MDA-MB-231, HCC-1143 and HCC-1937), and the ER+ cell line MCF-7 using confocal microscopy and Western blot analysis of pathway components. Effectiveness of five different Wnt pathway inhibitors (iCRT-3, iCRT-5, iCRT-14, IWP-4 and XAV-939) on cell
Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR) Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD)
Experimental evidence shows cross-talk in mammary cells between estrogen, insulin-like growth factor I (IGF-I) and their respective receptors and possible synergistic effects of estrogen receptor (ER) activation and increased IGF-I signaling with regard to breast tumor development, and epidemiological evidence suggests that circulating IGF-I levels may be related more to the risk of ER-positive than ER-negative breast cancer. Using a case-control study nested within the prospective European EPIC cohort (938 breast cancer cases and 1,394 matched control subjects), we analyzed the relationships of prediagnostic serum IGF-I levels with the risk of estrogen and progesterone receptor-positive and -negative breast tumors. IGF-I levels were positively associated with the risk of ER+ breast tumors overall (pre- and postmenopausal women combined, odds ratio (OR) Q4-Q1 = 1.41 [95% confidence interval (CI) 1.01-1.98] for the highest vs. lowest quartile; OR = 1.17 [95% CI 1.04-1.33] per 1-standard deviation (SD)
Breast cancer is one of the most common cancer deaths in female. Estrogen receptor(ER)-negative breast cancer constitutes approximately 30 % of breast cancer cases. Triple-negative is defined as a subgroup with ER, PR(progesterone receptor) and human epidermal growth factor receptor 2 (HER2) all negative. TNBC are assumed importance for its molecular characters, aggressive progress and distinct tranfer ability [1, 2]. Beneficial results of current anti-HER2 or hormonal therapy could not improve the curative effect of chemotherapy. In the absence of proper treatments, TNBC often progresses to metastatic lesions in the brain and lung in three years. Once being with metastasis, the 5-year survival rate of TNBC would be less than 30 %. Newly therapies are urgently needed to improve the prognosis for TNBC patients. Actually, TNBCs exhibit a high level of molecular heterogeneity without high-frequency driver mutations. About 60-70 % of TNBCs has mutations of p53. For PIK3CA mutations, it would be 11 ...
TY - JOUR. T1 - Estrogen receptor binding affinity and uterotrophic activity of triphenylhaloethylenes. AU - DeSombre, Eugene R.. AU - Mease, Ronnie C.. AU - Sanghavl, Jigi. AU - Singh, Tej. AU - Seevers, Robert H.. AU - Hughes, Alun. N1 - Funding Information: Acknowledgements-Wteh ank RestitutoD izon for his able supportin the animal studies,D r S. John Gatley for his analysiso f the metabolicp roductso f the diacetatesa, nd Johanna Darden for her help in preparationo f the manuscript. Supported by the NIH (CA27476, CA14599, HD15513), DOE Contract W-31-109-ENG-38a nd the Julius J. Reingold Fellowship Fund.. PY - 1988/6. Y1 - 1988/6. N2 - Radiohalogenated estrogens have considerable potential for estrogen receptor-directed imaging and therapy for cancers which contain such receptors. In an effort to evaluate the potential of the triphenyl ethylene structure for such purposes we have synthesized 3 series of 2-halosubstituted triphenylethylenes containing oxygen functions in the 4 position of both ...
[77 Pages Report] Check for Discount on Estrogen Receptor (ER Alpha or Estradiol Receptor or Nuclear Receptor Subfamily 3 Group A Member 1 or NR3A1 or ESR1) - Pipeline Review, H2 2017 report by Global Markets Direct. Estrogen Receptor (ER Alpha or Estradiol Receptor or Nuclear Receptor...
Objective To evaluate the frequency of the estrogen receptor (ER) gene PvuII and XbaI polymorphisms and their associations with bone mineral density (BMD) in a group of postmenopausal Turkish women. ...
Uncommon mutations in three genes in estrogen receptor positive breast cancer have a negative impact on disease prognosis reports a team of British and Australian researchers in |i||link https://www.nature.com/articles/s41467-018-05914-x|Nature Communications|/link|. |/i| |i||br /||/i|
Aromatase is one of the important target for drugs that interfere with production of estrogen in the treatment of estrogen receptor positive breast cancer. Therefore the discovery of novel aromatase inhibitors that can kill the growth of cancer cells selectively with minimal toxic effects on normal healthy cells is desirable. In the present study, novel 5-(4-bromophenyl)-1,3-oxazole derivatives were synthesized, characterized and screened for their biological effect. A series of novel 5-(4-bromophenyl)-1,3-oxazole derivatives OXZ-1 to 12 were docked by Auto Dock tool to evaluate their aromatase inhibition. All the derivatives were synthesized by using versatile and convenient route. Spectroscopic techniques have characterized the synthesized compounds in order to validate their structures. A total of 12 compounds were synthesized and evaluated for their in-vitro aromatase inhibitory activity and all derivatives were tested to assess their cytotoxic effect against breast cancer cell lines ...
This article reported on a rather large trial known as ATLAS that involved almost 7,000 women, from over 30 countries, with estrogen receptor positive breast cancer. They were randomized to tamoxifen for 10 years versus those who stopped after the traditional 5 year time period. The group who took tamoxifen for 10 years had less recurrence of their breast cancer even after they stopped tamoxifen at the 10 year time frame. In addition, there were fewer women who died in the group that took tamoxifen for 10 years versus those who took it for 5 years. There were slightly more cases of uterine cancer in the women who took tamoxifen for the extra 5 years. However, the number of deaths from this was much smaller than the incremental number of deaths from breast cancer.. ...
Estrogen receptor (ER) positive rates in breast cancer may be influenced by grade, stage, age and race. This study reviews the ER positive rates over a 15-year period at the University Malaya Medical Centre, Kuala Lumpur, Malaysia. Data on ER status of 3557 patients from 1994 to 2008 was analyzed. ER status was determined by immunohistochemistry with a cut-off point of 10%. ER positivity increased by about 2% for every 5-year cohort, from 54.5% in 1994-1998 to 58.4% in 2004-2008. Ethnicity and grade were significantly associated with ER positivity rates: Malay women were found to have a higher risk of ER negative tumors compared with Chinese women. Grade 1 cancers were nine times more likely to be ER positive compared with grade 3 cancers. In summary, the proportion of ER positive cancers increased with each time period, and ethnicity and grade were independent factors that influenced ER positive rates. ...
TY - JOUR. T1 - Estrogen receptor alpha signaling promotes Sle1-induced loss of tolerance and immune cell activation and is responsible for sex bias in B6.Sle1 congenic mice. AU - Yoachim, Shayla D. AU - Nuxoll, Jenny S.. AU - Bynoté, Kimberly K.. AU - Gould, Karen A. PY - 2015/6/1. Y1 - 2015/6/1. N2 - Sex bias in lupus incidence is thought to be due, in part, to the ability of estrogens to promote loss of tolerance. Previously, we showed that estrogens promote lupus via estrogen receptor α (ERα). C57BL/6 (B6) mice carrying the Sle1 lupus susceptibility locus (B6.Sle1) display loss of tolerance and develop anti-nuclear antibodies and immune cell hyperactivation. The incidence of loss of tolerance in B6.Sle1 females is greater than in males. Here, we show that a deficiency of either estrogens or ERα attenuates loss of tolerance and autoantibody development in B6.Sle1 females. Furthermore, we demonstrate that immune cell activation in B6.Sle1 mice shows sex bias and that ERα deficiency ...
Estrogen receptors (ERs) are steroid hormone receptors important in development, growth, and reproduction. The 2 well characterized ERs, alpha and beta, interact with a variety of receptor coregulators. These coregulators bind and direct the ERs to specific promoters, varying the ER target genes transcribed to modulate signaling responses. ERs play a large role in cancers of the female reproductive system, especially breast cancer. ER positive breast cancers can be treated with antiestrogen therapy, often yielding an improved prognosis. These types of treatments use selective estrogen receptor modulators to diminish side effects on other organs expressing estrogen receptors. In addition, estrogen signaling plays a role in other pathophysiological conditions such as osteoporosis and obesity. The mechanisms of estrogen receptor signaling are not entirely understood since there are many coregulators as well as a myriad of target genes ...
TY - JOUR. T1 - Prognostic Impact of HOTAIR Expression is Restricted to ER-Negative Breast Cancers. AU - Gökmen-Polar, Yesim. AU - Vladislav, I. Tudor. AU - Neelamraju, Yaseswini. AU - Janga, Sarath C.. AU - Badve, Sunil. PY - 2015. Y1 - 2015. N2 - Expression of HOX transcript antisense intergenic RNA (HOTAIR), a large intergenic noncoding RNA (lincRNA), has been described as a metastases-associated lincRNA in various cancers including breast, liver and colon cancer cancers. We sought to determine if expression of HOTAIR could be used as a surrogate for assessing nodal metastases and evaluated RNA in situ hybridization (RNA-ISH) assay in a tissue microarray constructed from 133 breast cancer patients. The prognostic value of HOTAIR was further validated in large cohorts using The Cancer Genome Atlas (TCGA) breast cancer subjects. RNA-ISH analysis was successful in 94 cases (17% cases scored 0, 32.9% scored 1, 30.8% scored 2, and 19.1% scored 3). The expression of HOTAIR did not correlate with ...
Background The aim of this retrospective study was to determine whether progesteron receptor (PgR) status have an influence on the prognosis of estrogen receptor positive (ER+)/HER2-negative breast carcinoma (BC).. Methods We retrospectively reviewed the medical files of 1680 operable BC patients (pts) diagnosed between 1996 and 2011 and 456 of whom ER,PgR and HER2 status known were included in this study. Patients were categorized into 2 groups; as group A (ER + /PgR-/HER2-negative) and group B (ER + /PgR + /HER2-negative). Twenty one percent (97 pts) of the pts were in group A.. Results Median follow up was 33.5 (0-177) months. Median age was 54 (21-90) years. Sixty-one percent (278) of the pts had node-positive BC. Sixty percent (276) of the pts were postmenopausal. Eighty percent (365) of the pts received adjuvant chemotherapy (ACT). Adjuvant hormonotherapy (AHT) was recommended to nearly all patients (mostly tamoxifen). Pts in group A had significantly higher lymph node positive disease as ...
The majority of breast cancers are also sensitive to estrogen, meaning that estrogen promotes tumor growth.. These cancers are called hormone receptor positive breast cancers.. For people with these cancers, treatments to lower estrogen levels or block estrogen production can be used to help prevent cancer recurrence after surgery, or to slow cancer growth.. According to Breast Cancer.org, alcohol can increase a womans risk of hormone-receptor-positive breast cancer.. Alcohol also enhances the effects of estrogen in driving the growth of breast cancer cells, according to 2016 research at the University of Houston.. Endometriosis is another estrogen-dependent disease.. Reducing estrogen levels and providing non-estrogen treatments have all been considered for the treatment of endometriosis.. The problem is that reducing the levels of estrogen in women can lead to infertility.. A study by the Womens Health Initiative showed that BY REDUCING HORMONES -. ( SPECIFICALLY ESTROGEN )- had significant ...
The majority of breast cancers are also sensitive to estrogen, meaning that estrogen promotes tumor growth.. These cancers are called hormone receptor positive breast cancers.. For people with these cancers, treatments to lower estrogen levels or block estrogen production can be used to help prevent cancer recurrence after surgery, or to slow cancer growth.. According to Breast Cancer.org, alcohol can increase a womans risk of hormone-receptor-positive breast cancer.. Alcohol also enhances the effects of estrogen in driving the growth of breast cancer cells, according to 2016 research at the University of Houston.. Endometriosis is another estrogen-dependent disease.. Reducing estrogen levels and providing non-estrogen treatments have all been considered for the treatment of endometriosis.. The problem is that reducing the levels of estrogen in women can lead to infertility.. A study by the Womens Health Initiative showed that BY REDUCING HORMONES -. ( SPECIFICALLY ESTROGEN )- had significant ...
From: NAME: Les Davies FUNC: Therapeutic Goods Admin TEL: (06)289 7182 - MDP 88 ,DAVIES LES at [email protected], To: mx%bioforum at [email protected] at [email protected] Message-id: D752IOD2V16Y From: NAME: Les Davies FUNC: Therapeutic Goods Admin TEL: (06)289 7182 - MDP 88 ,DAVIES LES at [email protected], Subject: (1) Estrogen receptor assays & (2) the nervous system Date: 04-Nov-1996 Posted-date: 04-Nov-1996 Precedence: 1 To: mx5biosci-request at [email protected] at [email protected] (1) Estrogen receptor assays Noted a reply to Raymond Pierre (from JS Amenta?) about receptor binding assays for estrogen receptors - the comment that the point is to inhibit non-specific binding and not affect the specific receptor binding is not really correct - non-specific binding is not inhibitable. In receptor binding assays, an excess of a known receptor binding compound is added (to a separate set of assay tubes from the control binding tubes) to make sure that specific receptors are fully saturated and then no tritiated label ...
The healthy breast is a tissue composed of centrally located milk producing glands connected to the nipple by ducts, surrounded by fat tissue and connective tissue. The growth of the breast is primarily mediated by the estrogens, while the androgens mediate tissue homeostasis and protect against growth signals. In breast cancer, the cells of the glands or ducts undergo malignant transformation, and start proliferating in an uncontrollable fashion. Breast cancer is the most common malignancy in women, and it is estimated that 10% of all women will be diagnosed with breast cancer during their life-time. The primary classification of breast cancer is based mainly on the expression of the estrogen receptor, and 70-80% of breast cancers are estrogen receptor positive, and are classified as luminal. The remaining breast cancers are classified into HER2 positive or triple negative breast cancer. Out of all breast cancers, ~80% are androgen receptor positive. This varies in different subtypes, however, ...
TY - JOUR. T1 - Alfa and beta estrogen receptors and the biliary tree. AU - Alvaro, Domenico. AU - Alpini, G.. AU - Onori, P.. AU - Franchitto, A.. AU - Glaser, S. S.. AU - Le Sage, G.. AU - Folli, F.. AU - Attili, A. F.. AU - Gaudio, E.. N1 - Funding Information: Supported by the grant MURST 2000 (40% funds) # MM06215421/2 and by an NIH grant DK58411 and by VA Merit Award to Dr. G. Alpini.. PY - 2002/7/31. Y1 - 2002/7/31. N2 - This manuscript summarizes recent data showing that estrogens and their receptors play an important role in modulating cholangiocyte proliferation. We have recently demonstrated that rat cholangiocytes express both estrogen receptors (ER)-α and -β subtypes, while hepatocytes only express ER-α. ER and especially the ER-β subtype, are overexpressed in cholangiocytes proliferating after bile duct ligation (BDL) in the rat, in association with enlarged bile duct mass and with enhanced estradiol serum levels. Cholangiocyte proliferation, during BDL, is impaired by estrogen ...
TY - JOUR. T1 - A gene expression signature from human breast cancer cells with acquired hormone independence identifies MYC as a mediator of antiestrogen resistance. AU - Miller, Todd W.. AU - Balko, Justin M.. AU - Ghazoui, Zara. AU - Dunbier, Anita. AU - Anderson, Helen. AU - Dowsett, Mitch. AU - González-Angulo, Ana M.. AU - Mills, Gordon B.. AU - Miller, William R.. AU - Wu, Huiyun. AU - Shyr, Yu. AU - Arteaga, Carlos L.. PY - 2011/4/1. Y1 - 2011/4/1. N2 - Purpose: Although most patients with estrogen receptor α (ER)-positive breast cancer initially respond to endocrine therapy, many ultimately develop resistance to antiestrogens. However, mechanisms of antiestrogen resistance and biomarkers predictive of such resistance are underdeveloped. Experimental Design: We adapted four ER+ human breast cancer cell lines to grow in an estrogen-depleted medium. A gene signature of estrogen independence was developed by comparing expression profiles of long-term estrogen-deprived (LTED) cells to ...
Recently in the pig hypothalamus a vasopressin- and oxytocin-containing nucleus was identified which, like the supraoptic nucleus, becomes sexually dimorphic after puberty. Following the increase in circulating steroids at puberty, the vasopressin- and oxytocin-containing nucleus becomes twice as large in both males and females. In adulthood, the vasopressin- and oxytocin-containing nucleus of females is approximately twice as large as that in males. Because these alterations are possibly due to an influence of gonadal steroids, i.e. estrogens, the vasopressin- and oxytocin-containing the presence of estrogen receptors. In addition to the area of the vasopressin- and oxytocin-containing nucleus, the present study documented the distribution of estrogen receptors in the septal area and other parts of the hypothalamus of intact post-pubertal male and female pigs, by utilizing immunocytochemical methodology. Intense nuclear estrogen receptor staining was found in a number of areas, i.e. the medial preoptic
TY - JOUR. T1 - Estrogen receptor α wields treatment-specific enhancers between morphologically similar endometrial tumors. AU - Droog, Marjolein. AU - Nevedomskaya, Ekaterina. AU - Dackus, Gwen M.. AU - Fles, Renske. AU - Kim, Yongsoo. AU - Hollema, Harry. AU - Mourits, Marian. AU - Nederlof, Petra M.. AU - Van Boven, Hester H.. AU - Linn, Sabine C.. AU - Van Leeuwen, Flora E.. AU - Wessels, Lodewyk F.A.. AU - Zwart, Wilbert. PY - 2017/2/21. Y1 - 2017/2/21. N2 - The DNA-binding sites of estrogen receptor α (ERα) show great plasticity under the control of hormones and endocrine therapy. Tamoxifen is a widely applied therapy in breast cancer that affects ERα interactions with coregulators and shifts the DNA-binding signature of ERα upon prolonged exposure in breast cancer. Although tamoxifen inhibits the progression of breast cancer, it increases the risk of endometrial cancer in postmenopausal women. We therefore asked whether the DNA-binding signature of ERα differs between endometrial ...
Receptors are proteins on cells that may attach to hormones that circulate in the blood. Normal breast cells and some breast cancer cells have receptors that attach to estrogen and progesterone. These two hormones often fuel the growth of breast cancer cells.. A biopsy can check to see if the cells have estrogen or progesterone receptors.. Cancer cells may contain neither, one, or both of these receptors. Breast cancers that contain estrogen receptors are called ER-positive (ER+) cancers, while those containing progesterone receptors are called PR-positive (PR+) cancers.. Women with hormone receptor-positive cancers tend to have a better prognosis and are much more likely to respond to hormone therapy than women with cancers without these receptors.. The ACS says that about one of five breast cancers have too much of a growth-promoting protein called HER2. The HER2 gene instructs the cells to make this protein. Tumors with increased levels of HER2 are referred to as HER2-positive.. Because ...
Breast cancer is a major cause of death worldwide. Human cytochrome P450 (CYP) 1B1 is a key enzyme in the metabolism of 17β-estradiol, and CYP1B1-metabolized 4-hydroxyestradiol is a marker for breast cancer. Furthermore, overexpression of cyclooxygenase-2 (COX-2), which produces prostaglandin E2 (PGE2), has been detected in invasive breast carcinomas. However, the interaction between PGE2 and CYP1B1 expression in human breast cancer is unclear. Here, we investigated the effect of PGE2 on CYP1B1 expression and its mechanism in breast cancer cells. PGE2 significantly increased CYP1B1 protein and messenger RNA expression and dose dependently enhanced CYP1B1 promoter activity in human breast cancer MCF-7 cells. Transient transfection with human CYP1B1 (hCYP1B1) deletion promoter constructs and cotreatment with inhibitors revealed that the estrogen response element contributed to the effects of PGE2. CYP1B1 expression was not affected by PGE2 in estrogen receptor (ER) α-negative MDA-MB-231 breast ...
Oncogenesis in breast cancer is often associated with excess estrogen receptor α(ERα) activation and overexpression of its coactivators. LRP16 is both an ERα target gene and an ERα coactivator, and plays a crucial role in ERα activation and proliferation of MCF-7 breast cancer cells. However, the regulation of the functional availability of this coactivator protein is not yet clear. Yeast two-hybrid screening, GST pulldown and coimmunoprecipitation (CoIP) identified the cytoplasmic intermediate filament protein keratin 18 (K18) as a novel LRP16-interacting protein. Fluorescence analysis revealed that GFP-tagged LRP16 was primarily localized in the nuclei of mock-transfected MCF-7 cells but was predominantly present in the cytoplasm of K18-transfected cells. Immunoblotting analysis demonstrated that the amount of cytoplasmic LRP16 was markedly increased in cells overexpressing K18 whereas nuclear levels were depressed. Conversely, knockdown of endogenous K18 expression in MCF-7 cells significantly
The amounts of estrogen receptor (ER) and progesterone receptor (PgR) in a primary tumor are predictive of the response to endocrine therapies of breast cancer. Several patients with ER-positive primary tumors relapse after adjuvant endocrine therapy with no ER expression in the recurrent tissue; much fewer with a recurrent disease after an ER-negative primary tumor may become endocrine responsive. These sequences of events indicate that a phenotype based on ER expression may not be a permanent feature of breast cancer. Ten patients with advanced breast cancer whose tumors overexpressed HER-2, but not ER or PgR, were treated with weekly trastuzumab at standard doses with or without chemotherapy. Three out of 10 patients showed overexpression of ERs first appearing after 9, 12 and 37 weeks, respectively, from the initiation of trastuzumab. Two of these patients were subsequently treated with endocrine therapy alone: one of them received letrozole for 3 years without evidence of progression. Therapeutic
The cytotoxic activity of PINO on human breast tumour cells is a debated issue. Previously, Chin et al. [25] described that PINO has a cytotoxic effect against MCF7 breast cancer cells (ED50 = 4.74 μM); however, in a later article [21], the same author found no cytotoxic effects. Surprisingly, the range of concentrations used in both studies was not specified. In addition, the cytotoxic effects of PINO in MDA-MB-231 cells have not been previously reported. In contrast, we tested a wide range of PINO concentrations and showed that there was cytotoxic activity at different concentrations in both human breast tumour cells tested. While PINO showed cytotoxic activity in both types of human breast tumour cells tested, the effect was more pronounced in negative oestrogen receptor tumour cells compared to oestrogen receptor-positive tumour cells (Figs. 4 and 5). In addition, for the first time, we describe the effects of PINO on human mammary epithelial cells. Our results suggest that PINO ranging ...