One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.
Cytoplasmic proteins that bind estrogens and migrate to the nucleus where they regulate DNA transcription. Evaluation of the state of estrogen receptors in breast cancer patients has become clinically important.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
Compounds that interact with ESTROGEN RECEPTORS in target tissues to bring about the effects similar to those of ESTRADIOL. Estrogens stimulate the female reproductive organs, and the development of secondary female SEX CHARACTERISTICS. Estrogenic chemicals include natural, synthetic, steroidal, or non-steroidal compounds.
The 17-beta-isomer of estradiol, an aromatized C18 steroid with hydroxyl group at 3-beta- and 17-beta-position. Estradiol-17-beta is the most potent form of mammalian estrogenic steroids.
A structurally diverse group of compounds distinguished from ESTROGENS by their ability to bind and activate ESTROGEN RECEPTORS but act as either an agonist or antagonist depending on the tissue type and hormonal milieu. They are classified as either first generation because they demonstrate estrogen agonist properties in the ENDOMETRIUM or second generation based on their patterns of tissue specificity. (Horm Res 1997;48:155-63)
Tumors or cancer of the human BREAST.
Compounds which inhibit or antagonize the action or biosynthesis of estrogenic compounds.
Substances that possess antiestrogenic actions but can also produce estrogenic effects as well. They act as complete or partial agonist or as antagonist. They can be either steroidal or nonsteroidal in structure.
One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
Specific proteins found in or on cells of progesterone target tissues that specifically combine with progesterone. The cytosol progesterone-receptor complex then associates with the nucleic acids to initiate protein synthesis. There are two kinds of progesterone receptors, A and B. Both are induced by estrogen and have short half-lives.
The surgical removal of one or both ovaries.
The hollow thick-walled muscular organ in the female PELVIS. It consists of the fundus (the body) which is the site of EMBRYO IMPLANTATION and FETAL DEVELOPMENT. Beyond the isthmus at the perineal end of fundus, is CERVIX UTERI (the neck) opening into VAGINA. Beyond the isthmi at the upper abdominal end of fundus, are the FALLOPIAN TUBES.
A cell line derived from cultured tumor cells.
Non-steroidal compounds with estrogenic activity.
Nucleotide sequences, usually upstream, which are recognized by specific regulatory transcription factors, thereby causing gene response to various regulatory agents. These elements may be found in both promoter and enhancer regions.
PLANT EXTRACTS and compounds, primarily ISOFLAVONES, that mimic or modulate endogenous estrogens, usually by binding to ESTROGEN RECEPTORS.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A pharmaceutical preparation containing a mixture of water-soluble, conjugated estrogens derived wholly or in part from URINE of pregnant mares or synthetically from ESTRONE and EQUILIN. It contains a sodium-salt mixture of estrone sulfate (52-62%) and equilin sulfate (22-30%) with a total of the two between 80-88%. Other concomitant conjugates include 17-alpha-dihydroequilin, 17-alpha-estradiol, and 17-beta-dihydroequilin. The potency of the preparation is expressed in terms of an equivalent quantity of sodium estrone sulfate.
Processes that stimulate the GENETIC TRANSCRIPTION of a gene or set of genes.
A molecule that binds to another molecule, used especially to refer to a small molecule that binds specifically to a larger molecule, e.g., an antigen binding to an antibody, a hormone or neurotransmitter binding to a receptor, or a substrate or allosteric effector binding to an enzyme. Ligands are also molecules that donate or accept a pair of electrons to form a coordinate covalent bond with the central metal atom of a coordination complex. (From Dorland, 27th ed)
An enzyme that catalyzes the desaturation (aromatization) of the ring A of C19 androgens and converts them to C18 estrogens. In this process, the 19-methyl is removed. This enzyme is membrane-bound, located in the endoplasmic reticulum of estrogen-producing cells of ovaries, placenta, testes, adipose, and brain tissues. Aromatase is encoded by the CYP19 gene, and functions in complex with NADPH-FERRIHEMOPROTEIN REDUCTASE in the cytochrome P-450 system.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in neoplastic tissue.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
Histochemical localization of immunoreactive substances using labeled antibodies as reagents.
Antineoplastic agents that are used to treat hormone-sensitive tumors. Hormone-sensitive tumors may be hormone-dependent, hormone-responsive, or both. A hormone-dependent tumor regresses on removal of the hormonal stimulus, by surgery or pharmacological block. Hormone-responsive tumors may regress when pharmacologic amounts of hormones are administered regardless of whether previous signs of hormone sensitivity were observed. The major hormone-responsive cancers include carcinomas of the breast, prostate, and endometrium; lymphomas; and certain leukemias. (From AMA Drug Evaluations Annual 1994, p2079)
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS; PROGESTERONE RECEPTORS; and THYROID HORMONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in the transcriptional activation of chromatin regions.
A synthetic nonsteroidal estrogen used in the treatment of menopausal and postmenopausal disorders. It was also used formerly as a growth promoter in animals. According to the Fourth Annual Report on Carcinogens (NTP 85-002, 1985), diethylstilbestrol has been listed as a known carcinogen. (Merck, 11th ed)
A transcription factor that partners with ligand bound GLUCOCORTICOID RECEPTORS and ESTROGEN RECEPTORS to stimulate GENETIC TRANSCRIPTION. It plays an important role in FERTILITY as well as in METABOLISM of LIPIDS.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Steroidal compounds related to ESTRADIOL, the major mammalian female sex hormone. Estradiol congeners include important estradiol precursors in the biosynthetic pathways, metabolites, derivatives, and synthetic steroids with estrogenic activities.
Certain tumors that 1, arise in organs that are normally dependent on specific hormones and 2, are stimulated or caused to regress by manipulation of the endocrine environment.
An estrogen responsive cell line derived from a patient with metastatic human breast ADENOCARCINOMA (at the Michigan Cancer Foundation.)
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
Benzene derivatives that include one or more hydroxyl groups attached to the ring structure.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
All of the processes involved in increasing CELL NUMBER including CELL DIVISION.
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories.
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A nuclear transcription factor. Heterodimerization with RETINOID X RECEPTOR GAMMA is important to metabolism of LIPIDS. It is the target of FIBRATES to control HYPERLIPIDEMIAS.
Strains of mice in which certain GENES of their GENOMES have been disrupted, or "knocked-out". To produce knockouts, using RECOMBINANT DNA technology, the normal DNA sequence of the gene being studied is altered to prevent synthesis of a normal gene product. Cloned cells in which this DNA alteration is successful are then injected into mouse EMBRYOS to produce chimeric mice. The chimeric mice are then bred to yield a strain in which all the cells of the mouse contain the disrupted gene. Knockout mice are used as EXPERIMENTAL ANIMAL MODELS for diseases (DISEASE MODELS, ANIMAL) and to clarify the functions of the genes.
Proteins, generally found in the CYTOPLASM, that specifically bind ANDROGENS and mediate their cellular actions. The complex of the androgen and receptor migrates to the CELL NUCLEUS where it induces transcription of specific segments of DNA.
Intracellular receptors that can be found in the cytoplasm or in the nucleus. They bind to extracellular signaling molecules that migrate through or are transported across the CELL MEMBRANE. Many members of this class of receptors occur in the cytoplasm and are transported to the CELL NUCLEUS upon ligand-binding where they signal via DNA-binding and transcription regulation. Also included in this category are receptors found on INTRACELLULAR MEMBRANES that act via mechanisms similar to CELL SURFACE RECEPTORS.
The simultaneous or sequential binding of multiple cell surface receptors to different ligands resulting in coordinated stimulation or suppression of signal transduction.
An interleukin-13 receptor subunit that is closely-related to the INTERLEUKIN-13 RECEPTOR ALPHA1 SUBUNIT. The receptor is found as a monomeric protein and has been considered to be a decoy receptor for interleukin-13 due the fact that it lacks cytoplasmic signaling domains.
An insecticide. Methoxychlor has estrogenic effects in mammals, among other effects.
A semisynthetic alkylated ESTRADIOL with a 17-alpha-ethinyl substitution. It has high estrogenic potency when administered orally, and is often used as the estrogenic component in ORAL CONTRACEPTIVES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
A nuclear receptor coactivator with specificity for ESTROGEN RECEPTORS and PROGESTERONE RECEPTORS. It contains a histone acetyltransferase activity that may play a role in CHROMATIN REMODELING during the process of nuclear receptor-induced transcription. The coactivator has been found at elevated levels in certain HORMONE-DEPENDENT NEOPLASMS such as those found in BREAST CANCER.
Compounds which contain the methyl radical substituted with two benzene rings. Permitted are any substituents, but ring fusion to any of the benzene rings is not allowed.
Proteins that enhance gene expression when associated with ligand bound activated NUCLEAR RECEPTORS. The coactivators may act through an enzymatic process that affects the rate of transcription or the structure of chromatin. Alternatively nuclear receptor coactivators can function as adaptor proteins that bring nuclear receptors into close proximity with transcriptional complexes.
A nuclear transcription factor. Heterodimerization with PPAR GAMMA is important in regulation of GLUCOSE metabolism and CELL GROWTH PROCESSES.
2- or 4-Hydroxyestrogens. Substances that are physiologically active in mammals, especially in the control of gonadotropin secretion. Physiological activity can be ascribed to either an estrogenic action or interaction with the catecholaminergic system.
Exogenous agents, synthetic and naturally occurring, which are capable of disrupting the functions of the ENDOCRINE SYSTEM including the maintenance of HOMEOSTASIS and the regulation of developmental processes. Endocrine disruptors are compounds that can mimic HORMONES, or enhance or block the binding of hormones to their receptors, or otherwise lead to activating or inhibiting the endocrine signaling pathways and hormone metabolism.
An interleukin receptor subunit with specificity for INTERLEUKIN-13. It dimerizes with the INTERLEUKIN-4 RECEPTOR ALPHA SUBUNIT to form the TYPE II INTERLEUKIN-4 RECEPTOR which has specificity for both INTERLEUKIN-4 and INTERLEUKIN-13. Signaling of this receptor subunit occurs through the interaction of its cytoplasmic domain with JANUS KINASES such as the TYK2 KINASE.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
The relationship between the dose of an administered drug and the response of the organism to the drug.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A technique for identifying specific DNA sequences that are bound, in vivo, to proteins of interest. It involves formaldehyde fixation of CHROMATIN to crosslink the DNA-BINDING PROTEINS to the DNA. After shearing the DNA into small fragments, specific DNA-protein complexes are isolated by immunoprecipitation with protein-specific ANTIBODIES. Then, the DNA isolated from the complex can be identified by PCR amplification and sequencing.
The period of cyclic physiological and behavior changes in non-primate female mammals that exhibit ESTRUS. The estrous cycle generally consists of 4 or 5 distinct periods corresponding to the endocrine status (PROESTRUS; ESTRUS; METESTRUS; DIESTRUS; and ANESTRUS).
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
The physiological period following the MENOPAUSE, the permanent cessation of the menstrual life.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Established cell cultures that have the potential to propagate indefinitely.
Proteins in the nucleus or cytoplasm that specifically bind RETINOIC ACID or RETINOL and trigger changes in the behavior of cells. Retinoic acid receptors, like steroid receptors, are ligand-activated transcription regulators. Several types have been recognized.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
The major progestational steroid that is secreted primarily by the CORPUS LUTEUM and the PLACENTA. Progesterone acts on the UTERUS, the MAMMARY GLANDS and the BRAIN. It is required in EMBRYO IMPLANTATION; PREGNANCY maintenance, and the development of mammary tissue for MILK production. Progesterone, converted from PREGNENOLONE, also serves as an intermediate in the biosynthesis of GONADAL STEROID HORMONES and adrenal CORTICOSTEROIDS.
Genes whose expression is easily detectable and therefore used to study promoter activity at many positions in a target genome. In recombinant DNA technology, these genes may be attached to a promoter region of interest.
CELL LINES derived from the CV-1 cell line by transformation with a replication origin defective mutant of SV40 VIRUS, which codes for wild type large T antigen (ANTIGENS, POLYOMAVIRUS TRANSFORMING). They are used for transfection and cloning. (The CV-1 cell line was derived from the kidney of an adult male African green monkey (CERCOPITHECUS AETHIOPS).)
High affinity receptors for THYROID HORMONES, especially TRIIODOTHYRONINE. These receptors are usually found in the nucleus where they regulate DNA transcription. They are encoded by the THRA gene (also known as NR1A1, THRA1, ERBA or ERBA1 gene) as several isoforms produced by alternative splicing.
A cell surface protein-tyrosine kinase receptor that is overexpressed in a variety of ADENOCARCINOMAS. It has extensive homology to and heterodimerizes with the EGF RECEPTOR, the ERBB-3 RECEPTOR, and the ERBB-4 RECEPTOR. Activation of the erbB-2 receptor occurs through heterodimer formation with a ligand-bound erbB receptor family member.
Plasma glycoprotein member of the serpin superfamily which inhibits TRYPSIN; NEUTROPHIL ELASTASE; and other PROTEOLYTIC ENZYMES.
Phospholipoglycoproteins produced in the fat body of egg-laying animals such as non-mammalian VERTEBRATES; ARTHROPODS; and others. Vitellogenins are secreted into the HEMOLYMPH, and taken into the OOCYTES by receptor-mediated ENDOCYTOSIS to form the major yolk proteins, VITELLINS. Vitellogenin production is under the regulation of steroid hormones, such as ESTRADIOL and JUVENILE HORMONES in insects.
Enzymes that catalyze acyl group transfer from ACETYL-CoA to HISTONES forming CoA and acetyl-histones.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
In humans, one of the paired regions in the anterior portion of the THORAX. The breasts consist of the MAMMARY GLANDS, the SKIN, the MUSCLES, the ADIPOSE TISSUE, and the CONNECTIVE TISSUES.
Enzymes that oxidize certain LUMINESCENT AGENTS to emit light (PHYSICAL LUMINESCENCE). The luciferases from different organisms have evolved differently so have different structures and substrates.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
The reproductive organ (GONADS) in female animals. In vertebrates, the ovary contains two functional parts: the OVARIAN FOLLICLE for the production of female germ cells (OOGENESIS); and the endocrine cells (GRANULOSA CELLS; THECA CELLS; and LUTEAL CELLS) for the production of ESTROGENS and PROGESTERONE.
Organic compounds containing the -CN radical. The concept is distinguished from CYANIDES, which denotes inorganic salts of HYDROGEN CYANIDE.
Compounds that inhibit AROMATASE in order to reduce production of estrogenic steroid hormones.
3-Phenylchromones. Isomeric form of FLAVONOIDS in which the benzene group is attached to the 3 position of the benzopyran ring instead of the 2 position.
A forkhead transcription factor that is an essential activator of GLUCAGON gene expression.
Different forms of a protein that may be produced from different GENES, or from the same gene by ALTERNATIVE SPLICING.
MAMMARY GLANDS in the non-human MAMMALS.
A positive regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
Those characteristics that distinguish one SEX from the other. The primary sex characteristics are the OVARIES and TESTES and their related hormones. Secondary sex characteristics are those which are masculine or feminine but not directly related to reproduction.
Elements of limited time intervals, contributing to particular results or situations.
The determination of the pattern of genes expressed at the level of GENETIC TRANSCRIPTION, under specific circumstances or in a specific cell.
Azoles of two nitrogens at the 1,2 positions, next to each other, in contrast with IMIDAZOLES in which they are at the 1,3 positions.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Tumors or cancer of ENDOMETRIUM, the mucous lining of the UTERUS. These neoplasms can be benign or malignant. Their classification and grading are based on the various cell types and the percent of undifferentiated cells.
Resistance or diminished response of a neoplasm to an antineoplastic agent in humans, animals, or cell or tissue cultures.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
The mucous membrane lining of the uterine cavity that is hormonally responsive during the MENSTRUAL CYCLE and PREGNANCY. The endometrium undergoes cyclic changes that characterize MENSTRUATION. After successful FERTILIZATION, it serves to sustain the developing embryo.
A highly chlorinated polycyclic hydrocarbon insecticide whose large number of chlorine atoms makes it resistant to degradation. It has been shown to be toxic to mammals and causes abnormal cellular changes in laboratory animals.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
Hypoxia-inducible factor 1, alpha subunit is a basic helix-loop-helix transcription factor that is regulated by OXYGEN availability and is targeted for degradation by VHL TUMOR SUPPRESSOR PROTEIN.
The interaction of two or more substrates or ligands with the same binding site. The displacement of one by the other is used in quantitative and selective affinity measurements.
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
Cytoplasmic proteins that bind estradiol, migrate to the nucleus, and regulate DNA transcription.
Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus.
Experimentally induced mammary neoplasms in animals to provide a model for studying human BREAST NEOPLASMS.
Small double-stranded, non-protein coding RNAs (21-31 nucleotides) involved in GENE SILENCING functions, especially RNA INTERFERENCE (RNAi). Endogenously, siRNAs are generated from dsRNAs (RNA, DOUBLE-STRANDED) by the same ribonuclease, Dicer, that generates miRNAs (MICRORNAS). The perfect match of the siRNAs' antisense strand to their target RNAs mediates RNAi by siRNA-guided RNA cleavage. siRNAs fall into different classes including trans-acting siRNA (tasiRNA), repeat-associated RNA (rasiRNA), small-scan RNA (scnRNA), and Piwi protein-interacting RNA (piRNA) and have different specific gene silencing functions.
Protein encoded by the bcl-1 gene which plays a critical role in regulating the cell cycle. Overexpression of cyclin D1 is the result of bcl-1 rearrangement, a t(11;14) translocation, and is implicated in various neoplasms.
Laboratory mice that have been produced from a genetically manipulated EGG or EMBRYO, MAMMALIAN.
Molecular products metabolized and secreted by neoplastic tissue and characterized biochemically in cells or body fluids. They are indicators of tumor stage and grade as well as useful for monitoring responses to treatment and predicting recurrence. Many chemical groups are represented including hormones, antigens, amino and nucleic acids, enzymes, polyamines, and specific cell membrane proteins and lipids.
An invasive (infiltrating) CARCINOMA of the mammary ductal system (MAMMARY GLANDS) in the human BREAST.
A potent androgenic steroid and major product secreted by the LEYDIG CELLS of the TESTIS. Its production is stimulated by LUTEINIZING HORMONE from the PITUITARY GLAND. In turn, testosterone exerts feedback control of the pituitary LH and FSH secretion. Depending on the tissues, testosterone can be further converted to DIHYDROTESTOSTERONE or ESTRADIOL.
An isoflavonoid derived from soy products. It inhibits PROTEIN-TYROSINE KINASE and topoisomerase-II (DNA TOPOISOMERASES, TYPE II); activity and is used as an antineoplastic and antitumor agent. Experimentally, it has been shown to induce G2 PHASE arrest in human and murine cell lines and inhibits PROTEIN-TYROSINE KINASE.
One of the two major pharmacological subdivisions of adrenergic receptors that were originally defined by the relative potencies of various adrenergic compounds. The alpha receptors were initially described as excitatory receptors that post-junctionally stimulate SMOOTH MUSCLE contraction. However, further analysis has revealed a more complex picture involving several alpha receptor subtypes and their involvement in feedback regulation.
Proteins whose abnormal expression (gain or loss) are associated with the development, growth, or progression of NEOPLASMS. Some neoplasm proteins are tumor antigens (ANTIGENS, NEOPLASM), i.e. they induce an immune reaction to their tumor. Many neoplasm proteins have been characterized and are used as tumor markers (BIOMARKERS, TUMOR) when they are detectable in cells and body fluids as monitors for the presence or growth of tumors. Abnormal expression of ONCOGENE PROTEINS is involved in neoplastic transformation, whereas the loss of expression of TUMOR SUPPRESSOR PROTEINS is involved with the loss of growth control and progression of the neoplasm.
Screening techniques first developed in yeast to identify genes encoding interacting proteins. Variations are used to evaluate interplay between proteins and other molecules. Two-hybrid techniques refer to analysis for protein-protein interactions, one-hybrid for DNA-protein interactions, three-hybrid interactions for RNA-protein interactions or ligand-based interactions. Reverse n-hybrid techniques refer to analysis for mutations or other small molecules that dissociate known interactions.
Cells that line the inner and outer surfaces of the body by forming cellular layers (EPITHELIUM) or masses. Epithelial cells lining the SKIN; the MOUTH; the NOSE; and the ANAL CANAL derive from ectoderm; those lining the RESPIRATORY SYSTEM and the DIGESTIVE SYSTEM derive from endoderm; others (CARDIOVASCULAR SYSTEM and LYMPHATIC SYSTEM) derive from mesoderm. Epithelial cells can be classified mainly by cell shape and function into squamous, glandular and transitional epithelial cells.
In vitro method for producing large amounts of specific DNA or RNA fragments of defined length and sequence from small amounts of short oligonucleotide flanking sequences (primers). The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. The reaction is efficient, specific, and extremely sensitive. Uses for the reaction include disease diagnosis, detection of difficult-to-isolate pathogens, mutation analysis, genetic testing, DNA sequencing, and analyzing evolutionary relationships.
A hydroxylated metabolite of ESTRADIOL or ESTRONE that has a hydroxyl group at C3, 16-alpha, and 17-beta position. Estriol is a major urinary estrogen. During PREGNANCY, a large amount of estriol is produced by the PLACENTA. Isomers with inversion of the hydroxyl group or groups are called epiestriol.
The status during which female mammals carry their developing young (EMBRYOS or FETUSES) in utero before birth, beginning from FERTILIZATION to BIRTH.
The largest family of cell surface receptors involved in SIGNAL TRANSDUCTION. They share a common structure and signal through HETEROTRIMERIC G-PROTEINS.
A receptor subunit that is a component of the TYPE I INTERLEUKIN-4 RECEPTOR and the TYPE II INTERLEUKIN-4 RECEPTOR. It signals through interaction of its cytoplasmic domain with JANUS KINASES such as JANUS KINASE 1.
17 beta-Hydroxy-4-androsten-3-ones. Testosterone derivatives formed by the substitution of one or more hydroxyl groups in any position.
Immunologic techniques based on the use of: (1) enzyme-antibody conjugates; (2) enzyme-antigen conjugates; (3) antienzyme antibody followed by its homologous enzyme; or (4) enzyme-antienzyme complexes. These are used histologically for visualizing or labeling tissue specimens.
Diffusible gene products that act on homologous or heterologous molecules of viral or cellular DNA to regulate the expression of proteins.
A nuclear protein that regulates the expression of genes involved in a diverse array of processes related to metabolism and reproduction. The protein contains three nuclear receptor interaction domains and three repressor domains and is closely-related in structure to NUCLEAR RECEPTOR CO-REPRESSOR 2.
An aromatized C18 steroid with a 3-hydroxyl group and a 17-ketone, a major mammalian estrogen. It is converted from ANDROSTENEDIONE directly, or from TESTOSTERONE via ESTRADIOL. In humans, it is produced primarily by the cyclic ovaries, PLACENTA, and the ADIPOSE TISSUE of men and postmenopausal women.
Proteins prepared by recombinant DNA technology.
The measurement of an organ in volume, mass, or heaviness.
The male gonad containing two functional parts: the SEMINIFEROUS TUBULES for the production and transport of male germ cells (SPERMATOGENESIS) and the interstitial compartment containing LEYDIG CELLS that produce ANDROGENS.
Ventral part of the DIENCEPHALON extending from the region of the OPTIC CHIASM to the caudal border of the MAMMILLARY BODIES and forming the inferior and lateral walls of the THIRD VENTRICLE.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
Derivatives of propionic acid. Included under this heading are a broad variety of acid forms, salts, esters, and amides that contain the carboxyethane structure.
Hybridization of a nucleic acid sample to a very large set of OLIGONUCLEOTIDE PROBES, which have been attached individually in columns and rows to a solid support, to determine a BASE SEQUENCE, or to detect variations in a gene sequence, GENE EXPRESSION, or for GENE MAPPING.
A CELL CYCLE and tumor growth marker which can be readily detected using IMMUNOCYTOCHEMISTRY methods. Ki-67 is a nuclear antigen present only in the nuclei of cycling cells.
Region of hypothalamus between the ANTERIOR COMMISSURE and OPTIC CHIASM.
The last menstrual period. Permanent cessation of menses (MENSTRUATION) is usually defined after 6 to 12 months of AMENORRHEA in a woman over 45 years of age. In the United States, menopause generally occurs in women between 48 and 55 years of age.
Steroid hormones produced by the GONADS. They stimulate reproductive organs, germ cell maturation, and the secondary sex characteristics in the males and the females. The major sex steroid hormones include ESTRADIOL; PROGESTERONE; and TESTOSTERONE.
The aglucon moiety of a saponin molecule. It may be triterpenoid or steroid, usually spirostan, in nature.
The genetic constitution of the individual, comprising the ALLELES present at each GENETIC LOCUS.
The process by which two molecules of the same chemical composition form a condensation product or polymer.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
A low affinity interleukin-5 receptor subunit that combines with the CYTOKINE RECEPTOR COMMON BETA SUBUNIT to form a high affinity receptor for INTERLEUKIN-5. Several isoforms of the interleukin-5 receptor alpha subunit exist due to multiple ALTERNATIVE SPLICING.
Proteins found usually in the cytoplasm or nucleus that specifically bind steroid hormones and trigger changes influencing the behavior of cells. The steroid receptor-steroid hormone complex regulates the transcription of specific genes.
The regular and simultaneous occurrence in a single interbreeding population of two or more discontinuous genotypes. The concept includes differences in genotypes ranging in size from a single nucleotide site (POLYMORPHISM, SINGLE NUCLEOTIDE) to large nucleotide sequences visible at a chromosomal level.
A potent androgenic metabolite of TESTOSTERONE. It is produced by the action of the enzyme 3-OXO-5-ALPHA-STEROID 4-DEHYDROGENASE.
A low affinity interleukin-11 receptor subunit that combines with the CYTOKINE RECEPTOR GP130 to form a high affinity receptor for INTERLEUKIN-11. Multiple isoforms of this protein exist due to ALTERNATIVE SPLICING of its MRNA.
A member of the NICOTINIC ACETYLCHOLINE RECEPTOR subfamily of the LIGAND-GATED ION CHANNEL family. It consists entirely of pentameric a7 subunits expressed in the CNS, autonomic nervous system, vascular system, lymphocytes and spleen.
Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs.
Proteins which maintain the transcriptional quiescence of specific GENES or OPERONS. Classical repressor proteins are DNA-binding proteins that are normally bound to the OPERATOR REGION of an operon, or the ENHANCER SEQUENCES of a gene until a signal occurs that causes their release.
A prediction of the probable outcome of a disease based on a individual's condition and the usual course of the disease as seen in similar situations.
Proteins that are normally involved in holding cellular growth in check. Deficiencies or abnormalities in these proteins may lead to unregulated cell growth and tumor development.
An electrophoretic technique for assaying the binding of one compound to another. Typically one compound is labeled to follow its mobility during electrophoresis. If the labeled compound is bound by the other compound, then the mobility of the labeled compound through the electrophoretic medium will be retarded.
Material prepared from plants.
Luciferases from RENILLA that oxidizes certain LUMINESCENT AGENTS to cause emission of PHOTONS.
An estrogen antagonist that has been used in the treatment of breast cancer.
Paired ducts in the human male through which semen is ejaculated into the urethra.
Promoter-specific RNA polymerase II transcription factor that binds to the GC box, one of the upstream promoter elements, in mammalian cells. The binding of Sp1 is necessary for the initiation of transcription in the promoters of a variety of cellular and viral GENES.
The rate dynamics in chemical or physical systems.
A subtype of RETINOIC ACID RECEPTORS that are specific for 9-cis-retinoic acid which function as nuclear TRANSCRIPTION FACTORS that regulate multiple signaling pathways.
Commonly observed structural components of proteins formed by simple combinations of adjacent secondary structures. A commonly observed structure may be composed of a CONSERVED SEQUENCE which can be represented by a CONSENSUS SEQUENCE.
Intercellular signaling peptides that were originally characterized by their ability to suppress NEOPLASM METASTASIS. Kisspeptins have since been found to play an important role in the neuroendocrine regulation of REPRODUCTION.
Compounds that interact with ANDROGEN RECEPTORS in target tissues to bring about the effects similar to those of TESTOSTERONE. Depending on the target tissues, androgenic effects can be on SEX DIFFERENTIATION; male reproductive organs, SPERMATOGENESIS; secondary male SEX CHARACTERISTICS; LIBIDO; development of muscle mass, strength, and power.
The aggregation of soluble ANTIGENS with ANTIBODIES, alone or with antibody binding factors such as ANTI-ANTIBODIES or STAPHYLOCOCCAL PROTEIN A, into complexes large enough to fall out of solution.
An intermediate in TESTOSTERONE biosynthesis, found in the TESTIS or the ADRENAL GLANDS. Androstenediol, derived from DEHYDROEPIANDROSTERONE by the reduction of the 17-keto group (17-HYDROXYSTEROID DEHYDROGENASES), is converted to TESTOSTERONE by the oxidation of the 3-beta hydroxyl group to a 3-keto group (3-HYDROXYSTEROID DEHYDROGENASES).
The period before MENOPAUSE. In premenopausal women, the climacteric transition from full sexual maturity to cessation of ovarian cycle takes place between the age of late thirty and early fifty.
A birth defect due to malformation of the URETHRA in which the urethral opening is below its normal location. In the male, the malformed urethra generally opens on the ventral surface of the PENIS or on the PERINEUM. In the female, the malformed urethral opening is in the VAGINA.
A gene silencing phenomenon whereby specific dsRNAs (RNA, DOUBLE-STRANDED) trigger the degradation of homologous mRNA (RNA, MESSENGER). The specific dsRNAs are processed into SMALL INTERFERING RNA (siRNA) which serves as a guide for cleavage of the homologous mRNA in the RNA-INDUCED SILENCING COMPLEX. DNA METHYLATION may also be triggered during this process.
Transport proteins that carry specific substances in the blood or across cell membranes.
Mutant mice homozygous for the recessive gene "nude" which fail to develop a thymus. They are useful in tumor studies and studies on immune responses.
The outward appearance of the individual. It is the product of interactions between genes, and between the GENOTYPE and the environment.
A small, unpaired gland situated in the SELLA TURCICA. It is connected to the HYPOTHALAMUS by a short stalk which is called the INFUNDIBULUM.
The material of CHROMOSOMES. It is a complex of DNA; HISTONES; and nonhistone proteins (CHROMOSOMAL PROTEINS, NON-HISTONE) found within the nucleus of a cell.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
The surgical removal of one or both testicles.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
A mediator complex subunit that is believed to play a key role in the coactivation of nuclear receptor-activated transcription by the mediator complex. It interacts with a variety of nuclear receptors including RETINOIC ACID RECEPTORS; THYROID HORMONE RECEPTORS; VITAMIN D RECEPTORS; PEROXISOME PROLIFERATOR-ACTIVATED RECEPTORS; ESTROGEN RECEPTORS; and GLUCOCORTICOID RECEPTORS.
An EPIDERMAL GROWTH FACTOR related protein that is found in a variety of tissues including EPITHELIUM, and maternal DECIDUA. It is synthesized as a transmembrane protein which can be cleaved to release a soluble active form which binds to the EGF RECEPTOR.
Refers to animals in the period of time just after birth.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
An integrin alpha subunit that primarily associates with INTEGRIN BETA1 or INTEGRIN BETA4 to form laminin-binding heterodimers. Integrin alpha6 has two alternatively spliced isoforms: integrin alpha6A and integrin alpha6B, which differ in their cytoplasmic domains and are regulated in a tissue-specific and developmental stage-specific manner.
Detection of RNA that has been electrophoretically separated and immobilized by blotting on nitrocellulose or other type of paper or nylon membrane followed by hybridization with labeled NUCLEIC ACID PROBES.
The network of channels formed at the termination of the straight SEMINIFEROUS TUBULES in the mediastinum testis. Rete testis channels drain into the efferent ductules that pass into the caput EPIDIDYMIS.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
A strain of albino rat developed at the Wistar Institute that has spread widely at other institutions. This has markedly diluted the original strain.
An amorphous form of carbon prepared from the incomplete combustion of animal or vegetable matter, e.g., wood. The activated form of charcoal is used in the treatment of poisoning. (Grant & Hackh's Chemical Dictionary, 5th ed)
Tumors or cancer of the MAMMARY GLAND in animals (MAMMARY GLANDS, ANIMAL).
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
Chemical substances that are foreign to the biological system. They include naturally occurring compounds, drugs, environmental agents, carcinogens, insecticides, etc.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.

Dominant activity of activation function 1 (AF-1) and differential stoichiometric requirements for AF-1 and -2 in the estrogen receptor alpha-beta heterodimeric complex. (1/3532)

Estrogenic responses are now known to be mediated by two forms of estrogen receptors (ER), ERalpha and ERbeta, that can function as homodimers or heterodimers. As homodimers the two have been recently shown to exhibit distinct transcriptional responses to estradiol (E2), antiestrogens, and coactivators, suggesting that the ER complexes are not functionally equivalent. However, because the three possible configurations of ER complexes all recognize the same estrogen response element, it has not been possible to evaluate the transcriptional properties of the ER heterodimer complex by transfection assays. Using ER subunits with modified DNA recognition specificity, we were able to measure the transcriptional properties of ERalpha-ERbeta heterodimers in transfected cells without interference from the two ER homodimer complexes. We first demonstrated that the individual activation function 1 (AF-1) domains act in a dominant manner within the ERalpha-ERbeta heterodimer: the mixed agonist-antagonist 4-hydroxytamoxifen acts as an agonist in a promoter- and cell context-dependent manner via the ERalpha AF-1, while activation of the complex by the mitogen-activated protein kinase (MAPK) pathway requires only the ERalpha- or ERbeta-responsive MAPK site. Using ligand-binding and AF-2-defective mutants, we further demonstrated that while the ERalpha-ERbeta heterodimer can be activated when only one E2-binding competent partner is present per dimer, two functional AF-2 domains are required for transcriptional activity. Taken together, the results of this study of a retinoid X receptor-independent heterodimer complex, the first such study, provide evidence of different stoichiometric requirements for AF-1 and -2 activity and demonstrate that AF-1 receptor-specific properties are maintained within the ERalpha-ERbeta heterodimer.  (+info)

Localization of curved DNA and its association with nucleosome phasing in the promoter region of the human estrogen receptor alpha gene. (2/3532)

We determined DNA bend sites in the promoter region of the human estrogen receptor (ER) gene by the circular permutation assay. A total of five sites (ERB-4 to -1, and ERB+1) mapped in the 3 kb region showed an average distance of 688 bp. Most of the sites were accompanied by short poly(dA) x poly(dT) tracts including the potential bend core sequence A2N8A2N8A2 (A/A/A). Fine mapping of the ERB-2 site indicated that this A/A/A and the 20 bp immediate flanking sequence containing one half of the estrogen response element were the sites of DNA curvature. All of the experimentally mapped bend sites corresponded to the positions of DNA curvature as well as to nucleosomes predicted by computer analysis. In vitro nucleosome mapping at ERB-2 revealed that the bend center was located 10-30 bp from the experimental and predicted nucleosome dyad axes.  (+info)

Expression of oestrogen receptor alpha and beta mRNA in corpus luteum of human subjects. (3/3532)

To investigate the role of oestrogen receptor beta (ERbeta) in the function of human ovarian corpus luteum, the levels of luteal ERalpha and ERbeta mRNA were determined using competitive reverse transcription-polymerase chain reaction-Southern blot analysis. The expression of ERalpha and ERbeta mRNA was detected in all luteal samples analysed. Luteal ERalpha and ERbeta mRNA levels were significantly lower (P<0.01 and P<0.05 respectively) at the late secretory phase than those at the early and mid-secretory phases of the endometrium. The ratio of ERalpha to ERbeta mRNA levels showed no change during the secretory phase of the endometrium. This study demonstrates that ERbeta is co-expressed with ERalpha in human corpus luteum and is likely to play a biological role in the regulation of steroidal action of the corpus luteum with ERalpha.  (+info)

Oestrogen receptor-alpha variant mRNA expression in primary human breast tumours and matched lymph node metastases. (4/3532)

We have shown previously that the relative expression of a truncated oestrogen receptor-alpha variant mRNA (ER clone 4) is significantly increased in axillary node-positive primary breast tumours compared with node-negative tumours. In this study, we have examined the relative expression of clone 4-truncated, exon 5-deleted and exon 7-deleted oestrogen receptor-alpha variant mRNAs in 15 primary breast tumour samples and in synchronous axillary lymph node metastases. Overall, there were no significant differences between the primary tumours and the matched metastases in the relative expression of these three specific variant mRNAs. Furthermore, the pattern of all deleted oestrogen receptor-alpha variant mRNAs appeared conserved between any primary and its matched secondary tumour.  (+info)

Disruption of estrogen signaling does not prevent progesterone action in the estrogen receptor alpha knockout mouse uterus. (5/3532)

Estrogen is known to increase progesterone receptor (PR) levels in the wild-type mouse uterus, and this estrogen induction was thought to be important for progesterone action through the PR. The estrogen receptor alpha knockout (ERKO) mouse uterus was observed to express PR mRNA that cannot be induced by estrogen. Progesterone action was characterized to determine whether it was diminished in ERKO mice. The PR protein is present in the ERKO uterus at 60% of the level measured in a wild-type uterus. The PR-A and PR-B isoforms are both detected on Western blot, and the ratio of isoforms is the same in both genotypes. Although the level of PR is reduced in the ERKO uterus, the receptor level is sufficient to induce genomic responses, since both calcitonin and amphiregulin mRNAs were increased after progesterone treatment. Finally, the ERKO uterus can be induced to undergo a progesterone-dependent decidual response. Surprisingly, the decidual response is estrogen independent in the ERKO, although it remains estrogen dependent in a wild type. These results indicate that estrogen receptor alpha modulation of PR levels is not necessary for expression of the PR or genomic and physiologic responses to progesterone in the ERKO uterus.  (+info)

Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. (6/3532)

Estrogen receptor (ER) modulators produce distinct tissue-specific biological effects, but within the confines of the established models of ER action it is difficult to understand why. Previous studies have suggested that there might be a relationship between ER structure and activity. Different ER modulators may induce conformational changes in the receptor that result in a specific biological activity. To investigate the possibility of modulator-specific conformational changes, we have applied affinity selection of peptides to identify binding surfaces that are exposed on the apo-ERs alpha and beta and on each receptor complexed with estradiol or 4-OH tamoxifen. These peptides are sensitive probes of receptor conformation. We show here that ER ligands, known to produce distinct biological effects, induce distinct conformational changes in the receptors, providing a strong correlation between ER conformation and biological activity. Furthermore, the ability of some of the peptides to discriminate between different ER alpha and ER beta ligand complexes suggests that the biological effects of ER agonists and antagonists acting through these receptors are likely to be different.  (+info)

A mouse mammary tumor virus-Wnt-1 transgene induces mammary gland hyperplasia and tumorigenesis in mice lacking estrogen receptor-alpha. (7/3532)

Estrogens have important functions in mammary gland development and carcinogenesis. To better define these roles, we have used two previously characterized lines of genetically altered mice: estrogen receptor-alpha (ER alpha) knockout (ERKO) mice, which lack the gene encoding ER alpha, and mouse mammary virus tumor (MMTV)-Wnt-1 transgenic mice (Wnt-1 TG), which develop mammary hyperplasia and neoplasia due to ectopic production of the Wnt-1 secretory glycoprotein. We have crossed these lines to ascertain the effects of ER alpha deficiency on mammary gland development and carcinogenesis in mice expressing the Wnt-1 transgene. Introduction of the Wnt-1 transgene into the ERKO background stimulates proliferation of alveolar-like epithelium, indicating that Wnt-1 protein can promote mitogenesis in the absence of an ER alpha-mediated response. The hyperplastic glandular tissue remains confined to the nipple region, implying that the requirement for ER alpha in ductal expansion is not overcome by ectopic Wnt-1. Tumors were detected in virgin ERKO females expressing the Wnt-1 transgene at an average age (48 weeks) that is twice that seen in virgin Wnt-1 TG mice (24 weeks) competent to produce ER alpha. Prepubertal ovariectomy of Wnt-1 TG mice also extended tumor latency to 42 weeks. However, pregnancy did not appear to accelerate the appearance of tumors in Wnt-1 TG mice, and tumor growth rates were not measurably affected by late ovariectomy. Small hyperplastic mammary glands were observed in Wnt-1 TG males, regardless of ER alpha gene status; the glands were similar in appearance to those found in ERKO/Wnt-1 TG females. Mammary tumors also occurred in Wnt-1 TG males; latency tended to be longer in the heterozygous ER alpha and ERKO males (86 to 100 weeks) than in wild-type ER alpha mice (ca. 75 weeks). We conclude that ectopic expression of the Wnt-1 proto-oncogene can induce mammary hyperplasia and tumorigenesis in the absence of ER alpha in female and male mice. The delayed time of tumor appearance may depend on the number of cells at risk of secondary events in the hyperplastic glands, on the carcinogenesis-promoting effects of ER alpha signaling, or on both.  (+info)

Expression of human estrogen receptor-alpha and -beta, progesterone receptor, and androgen receptor mRNA in normal and malignant ovarian epithelial cells. (8/3532)

Our understanding of the roles played by sex hormones in ovarian carcinogenesis has been limited by a lack of data concerning the mode of sex hormone action in human ovarian surface epithelial (HOSE) cells, the tissue of origin of >90% of ovarian cancers. We have compared the relative abundance of estrogen receptor (ER)alpha, ERbeta, progesterone receptor (PR), and androgen receptor (AR) mRNA in four primary cultures of HOSE cells obtained from postmenopausal women to those found in late serous adenocarcinoma primary cell cultures and established ovarian cancer cell lines. We observed coexpression of ERalpha and ERbeta mRNA along with AR and PR transcripts in normal HOSE cells and disruption of ERalpha mRNA expression as well as dramatic down-regulation of PR and AR transcript expression in most ovarian cancer cells. In contrast, levels of ERbeta mRNA were unaffected by the malignant state. Additionally, a novel mutation involving a 32-bp deletion in exon 1 of ERalpha transcripts was detected in the SKOV3 cell line. This mutation would explain why SKOV3 was reported to be ER-positive but estrogen-insensitive. Taken together, these findings suggest that estrogens, signaling via either or both ER subtypes, may play an indispensable role in regulating normal HOSE cell functions. Therefore, loss of ERalpha, PR, and AR mRNA expression in HOSE cells may be responsible for neoplastic transformation in this cell type. In contrast, the roles played by ERbeta in normal and malignant HOSE cells remain elusive. Finally, the coexistence of mutated ERalpha mRNA and normal ERbeta transcripts in SKOV3 argues in favor of a dependency of ERbeta action on functional ERalphas.  (+info)

The results presented here demonstrate that p53 upregulates estrogen receptor-alpha (ER alpha) expression in the human breast cancer cell line MCF-7. Two approaches were used to alter the activity of p53 in the cells. In the first approach, stable transfectants expressing an antisense p53 were established. In the stable clones, expression of antisense p53 resulted in a decrease in the expression of ER alpha protein. In the second approach, MCF-7 cells were transiently transfected with wild-type p53. Overexpression of p53 increased the amount of ER alpha. To determine whether the effects of p53 on the expression of ER alpha were due to changes in transcription, deletion mutants of the ER alpha promoter were used. This experimental approach demonstrated that p53 up-regulates ER alpha gene expression by increasing transcription of the gene through elements located upstream of promoter A. Transfection assays using p53 mutants further demonstrated that the p53-induced increase in ER alpha gene ...
Loss of estrogen receptor α (ERα) expression and gain of TWIST (TWIST1) expression in breast tumors correlate with increased disease recurrence and metastasis and poor disease-free s...
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TY - JOUR. T1 - The estrogen receptors alpha, beta, and beta cx. AU - Shaaban, Abeer M. AU - Speirs, Valerie. PY - 2005/11/15. Y1 - 2005/11/15. KW - Breast. KW - Breast Neoplasms. KW - Carcinoma in Situ. KW - Carcinoma, Ductal, Breast. KW - Estrogen Receptor alpha. KW - Estrogen Receptor beta. KW - Female. KW - Humans. KW - Immunohistochemistry. KW - Protein Isoforms. KW - Receptors, Estrogen. KW - Comment. KW - Comparative Study. KW - Letter. U2 - 10.1158/1078-0432.CCR-05-1446. DO - 10.1158/1078-0432.CCR-05-1446. M3 - Article. C2 - 16299256. VL - 11. SP - 8222; author reply 8222-3. JO - Clinical Cancer Research. JF - Clinical Cancer Research. SN - 1078-0432. IS - 22. ER - ...
BACKGROUND: Estrogen acutely activates endothelial nitric oxide synthase (eNOS). However, the identity of the receptors involved in this rapid response remains unclear. METHODS AND RESULTS: We detected an estrogen receptor alpha (ERalpha) transcript in human endothelial cells that encodes a truncated 46-kDa ERalpha (Delta1a-hERalpha-46). A corresponding 46-kDa ERalpha protein was identified in endothelial cell lysates. Transfection of cDNAs encoding the full-length ERalpha (ERalpha-66) and Delta1a-hERalpha-46 resulted in appropriately sized recombinant proteins identified by anti-ERalpha antibodies. Confocal microscopy revealed that a proportion of both ERalpha-66 and hERalpha-46 was localized outside the nucleus and mediated specific cell-surface binding of estrogen as assessed by FITC-conjugated, BSA-estrogen binding studies. Both ERalpha isoforms colocalized with eNOS and mediated acute activation of eNOS in response to estrogen stimulation. However, estrogen-stimulated transcriptional activation
BACKGROUND: Estrogen acutely activates endothelial nitric oxide synthase (eNOS). However, the identity of the receptors involved in this rapid response remains unclear. METHODS AND RESULTS: We detected an estrogen receptor alpha (ERalpha) transcript in human endothelial cells that encodes a truncated 46-kDa ERalpha (Delta1a-hERalpha-46). A corresponding 46-kDa ERalpha protein was identified in endothelial cell lysates. Transfection of cDNAs encoding the full-length ERalpha (ERalpha-66) and Delta1a-hERalpha-46 resulted in appropriately sized recombinant proteins identified by anti-ERalpha antibodies. Confocal microscopy revealed that a proportion of both ERalpha-66 and hERalpha-46 was localized outside the nucleus and mediated specific cell-surface binding of estrogen as assessed by FITC-conjugated, BSA-estrogen binding studies. Both ERalpha isoforms colocalized with eNOS and mediated acute activation of eNOS in response to estrogen stimulation. However, estrogen-stimulated transcriptional activation
A novel estrogen receptor (ER)alpha coactivator complex, the MLL2 complex, which consists of MLL2, ASH2, RBQ3, and WDR5, was identified. ERalpha directly binds to the MLL2 complex through two LXXLL motifs in a region of MLL2 near the C terminus in a ligand-dependent manner. Disrupting the interaction between ERalpha and the MLL2 complex with small interfering RNAs specific against MLL2 or an MLL2 fragment representing the interacting region with ERalpha significantly inhibited the ERalpha transcription activity. The MLL2 complex was recruited on promoters of ERalpha target genes along with ERalpha upon estrogen stimulation. Inhibition of MLL2 expression decreased the estrogen-induced expression of ERalpha target genes cathepsin D and to a lesser extent pS2. In addition, MCF-7 cell growth was also inhibited by the depletion of MLL2. These results demonstrate that the ERalpha signaling pathway is critically dependent on its direct interaction with the MLL2 complex and suggest a central
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 ...
Endocrine therapies focus on the service of the oestrogen receptor alpha dog (Emergency room) via distinct systems, but it all is not very clear whether breasts tumor cells may adapt to treatment using drug-specific systems. development. Finally, we demonstrate that a CB-based personal might become utilized to improve the stratification of Emergency room breast cancer individuals before adjuvant treatment. Outcomes Version to AI treatment qualified prospects to invasiveness ETs are designed to stop oestrogen-driven expansion by interfering with one particular TF (for example, Emergency room). Nevertheless, we hypothesized that the advancement of level of resistance may follow specific ways and generate alternate phenotypes through the different molecular systems particular to each agent2. To check this speculation, we utilized a series of isogenic cell lines resistant to solitary real estate agents or a mixture of real estate agents (endocrine therapy (ET)-resistant ETR cells, Fig. 1a)15. Our ...
Estrogen is essential for the development and maintenance of optimal bone mass in women and men, and acts through activation of estrogen receptors (ER). We have examined the pathways of estrogen action on the skeleton by seeking to localize the classical estrogen receptor, ER alpha, to particular cells to test the hypotheses that 1) estrogen directly influences growth plate chondrocytes; and 2) estrogen has a principal action on bone tissue via osteoblasts. ER alpha messenger ribonucleic acid (mRNA) was localized by in situ hybridization in human specimens from five males (11-15 yr old), two females (9 and 11 yr old), and three growing rabbits. In all of the human material examined, ER alpha mRNA was consistently identified in chondrocytes. In all of the rabbit tissue studied, ER alpha mRNA was localized in chondrocytes of the growth plate and the subarticular epiphyseal growth center. ER alpha mRNA signals were readily observed in both active osteoblasts and lining cells on trabecular surfaces of all
In mammalian cells, the level of estrogen receptor alpha (ER alpha) is rapidly decreased upon estrogen treatment, and this regulation involves proteasome degradation. Using different approaches, we showed that the Mdm2 oncogenic ubiquitin-ligase directly interacts with ER alpha in a ternary complex with p53 and is involved in the regulation of ER alpha turnover (both in the absence or presence of estrogens). Several lines of evidence indicated that this effect of Mdm2 required its ubiquitin-ligase activity and involved the ubiquitin/proteasome pathway. Moreover, in MCF-7 human breast cancer cells, various p53-inducing agents (such as UV irradiation) or treatment with RITA (which inhibits the interaction of p53 with Mdm2) stabilized ER alpha and abolished its 17 beta-estradiol-dependent turnover. Interestingly, our data indicated that ligand-dependent receptor turnover was not required for efficient transactivation. Altogether, our results indicate that the Mdm2 oncoprotein and stress-inducing ...
Jessop, H L and Sjoberg, M and Cheng, M Z and Zaman, G and Wheeler-Jones, C P D and Lanyon, L E (2001) Mechanical strain and estrogen activate estrogen receptor alpha in bone cells. JOURNAL OF BONE AND MINERAL RESEARCH, 16 (6). pp. 1045-1055. ...
TY - JOUR. T1 - aP2-Cre-mediated inactivation of estrogen receptor alpha causes hydrometra. AU - Antonson, Per. AU - Matic, Marko. AU - Portwood, Neil. AU - Kuiper, Raoul V.. AU - Bryzgalova, Galyna. AU - Gao, Hui. AU - Windahl, Sara H.. AU - Humire, Patricia. AU - Ohlsson, Claes. AU - Berggren, Per Olof. AU - Gustafsson, Jan Åke. AU - Dahlman-Wright, Karin. PY - 2014/1/8. Y1 - 2014/1/8. N2 - In this study we describe the reproductive phenotypes of a novel mouse model in which Cre-mediated deletion of ERα is regulated by the aP2 (fatty acid binding protein 4) promoter. ERα-floxed mice were crossed with transgenic mice expressing Cre-recombinase under the control of the aP2 promoter to generate aP2-Cre/ERαflox/flox mice. As expected, ERα mRNA levels were reduced in adipose tissue, but in addition we also detected an 80% reduction of ERα levels in the hypothalamus of aP2-Cre/ ERαflox/flox mice. Phenotypic analysis revealed that aP2-Cre/ERαflox/flox female mice were infertile. In line with ...
6HHP: Ternary complex of Estrogen Receptor alpha peptide and 14-3-3 sigma C42 mutant bound to disulfide fragment PPI stabilizer 1
Rabbit polyclonal Estrogen Receptor alpha (phospho S104 + S106) antibody. Validated in IHC and tested in Rat. Immunogen corresponding to synthetic peptide.
Human estrogen receptor alpha (hERα) is a hormone-responsive nuclear receptor (NR) involved in cell growth and survival that contains both a DNA-binding domain (DBD) and a ligand-binding domain (LBD). Functionally relevant inter-domain interactions between the DBD and LBD have been observed in sever …
Estrogen receptor-alpha (ER alpha) is downregulated in the presence of its cognate ligand, estradiol (E2), through the ubiquitin proteasome pathway. Here, we show that ubiquitin proteasome function is required for ER alpha to serve as a transcriptional activator. Deletion of the last 61 amino acids …
Background Breast cancer is currently classified in 3 groups based on estrogen receptor alpha (ER) and human epidermal growth factor receptor 2 (HER2/ERBB2) gene expression: one basal-like (ER-ERBB2-), one HER2−enriched (ERBB2+) and one luminal (ER+). Yet, in transcriptome-based classifications, ER-ERBB2+ group partially overlaps with more recently defined ER-AR+ (androgen receptor positive) group. This type was named molecular apocrine, in reference to the histopathologically characterized apocrine carcinomas (H-Apo), in which a marked activation of AR signaling was demonstrated with a distinct proteomic signature. H-Apo tumors correspond to 1% of invasive breast carcinomas and are clearly morphological distinct from other AR+ tumors. However, no specific H-Apo transcriptome signature has been reported for this sub-group. In an effort to better characterize those tumors, we have performed a meta-analysis of genomic data, focusing on the ER- AR+ breast subset.. Samples and Methods: Chips were ...
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Alternative splicing is critical for generating complex proteomes in response to extracellular signals. Nuclear receptors including estrogen receptor alpha (ERα) and their ligands promote alternative splicing. The endogenous targets of ERα:estradiol (E2)-mediated alternative splicing and the influence of extracellular kinases that phosphorylate ERα on E2-induced splicing are unknown. MCF-7 and its anti-estrogen derivatives were used for the majority of the assays. CD44 mini gene was used to measure the effect of E2 and AKT on alternative splicing. ExonHit array analysis was performed to identify E2 and AKT-regulated endogenous alternatively spliced apoptosis-related genes. Quantitative reverse transcription polymerase chain reaction was performed to verify alternative splicing. ERα binding to alternatively spliced genes was verified by chromatin immunoprecipitation assay. Bromodeoxyuridine incorporation-ELISA and Annexin V labeling assays were done to measure cell proliferation and apoptosis,
Comprehensive evaluation of the estrogen receptor alpha gene reveals further evidence for association with type 2 diabetes enriched for nephropathy in an African American population. ...
Phase 1 of the study will be conducted to determine the maximum tolerated dose (MTD) and/or the recommended Phase 2 dose (RP2D) of H3B-6545 in women with
Commander Estrogen Receptor alpha anticorps monoclonal et polyclonal pour beaucoup dapplications. Selection de fournisseur de qualité pour anti-Estrogen Receptor alpha anticorps.
Approximately 75% of breast cancers are estrogen receptor (ERα) positive, underscoring the dependence of cancer cells on estrogen for growth and survival. Patients treated with endocrine therapy often develop resistance, either de novo or acquired, which is caused by aberrations within the growth factor signaling pathways. The mechanistic target of rapamycin complex 1 (mTORC1) has emerged as a critical node in estrogenic signaling. We have previously shown that mTORC1 can phosphorylate and activate ERα on S167 via its effector the 40S ribosomal S6 kinase 1 (S6K1). Presently, we have uncovered a direct link between mTORC1 and ERα. We found that ERα binds to regulatory-associated protein of mTOR (Raptor) and causes it to translocate to the nucleus upon estrogen stimulation. Additionally, we identified mTOR as the kinase that directly phosphorylates ERα and activates transcription of ER target genes. Our findings show a direct link between mTORC1 and ERα, which further implicates mTORC1 ...
Rabbit polyclonal Estrogen Receptor alpha antibody validated for WB, IHC and tested in Human and Mouse. Immunogen corresponding to synthetic peptide
Estrogen Receptor alpha兔多克隆抗体可与小鼠, 人样本反应并经WB, ELISA, IHC实验严格验证,被4篇文献引用并得到1个独立的用户反馈。
AS05 065 Aquaculture antibodies, antibodies to fish stress proteins, estrogen receptor, antibodies to estrogen receptor alpha and beta,PO3372, Q92731, nuclear receptor subfamily 3 group A member 2 antibody
Endocrine therapy is an effective option for the treatment of estrogen receptor alpha (ERα)-positive breast cancers. Unfortunately, a large fraction of women ...
Alonso A, Fernandez R, Ordanyonez P, Moreno M, Patterson buy cardarone safely online AM, et al. (2006) Regulation of estrogen receptor alpha past estradiol in buy generic cardarone pregnant and estradiol treated rats. Steroids. However, our information showed no interchange in buy generic cardarone GSK3 phosphorylation associated with decreased apartment viability induced at Akt2 and Akt3 disruption. Figure 1 Photochemistry parameters circumspect using the DualPAM. Immediately after the lay unrestricted pressed a button, the corresponding discs on the screen were switched to green (if dominates chose the right button, a hit) or to red (if fields chose a ended of the average button, an error). There was also a nonsignificant gain in amount survival (OS). For example, the examine showed that barely 83% of hospitals utilize automated dispensing cabinets as into a receive of their distribution model; 10% utilize robotic dispensing. The opportunity regions directorial conducive to largeness ...
Abstract: Alnustone-like compounds are promising inhibitors for estrogen receptor \alpha (ER-\alpha), which is a novel cancer therapeutic target. Therefore, 10 alnustone-like compounds with substituents at the phenyl rings ...
Studies with live cells demonstrate that agonist and antagonist rapidly (within minutes) modulate the subnuclear dynamics of estrogen receptor alpha (ER) and st
Barone I, Brusco L, Gu G, Selever J, Beyer A, Covington KR, Tsimelzon A, Wang T, Hilsenbeck SG, Chamness GC, Andò S, Fuqua SAW. Loss of Rho GDIα and resistance to tamoxifen via effects on estrogen receptor α. J Natl Cancer Inst. 2011 ;103(7):538-52. ...
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 ...
The transition to the postmenopausal stage is associated with an increased risk for vascular diseases, including myocardial infarction and stroke. This has been linked to a decrease in estrogen production. Estrogens mediate their effects on the brain to a major extent through binding to nuclear receptors, estrogen receptor alpha and beta. It is possible that positive and adverse effects of estrogens are related to interactions between receptor genotypes and hormones. Notably, the estrogen receptor alpha polymorphism c 454-397T/T is associated with increased risk of hemorrhagic stroke, with a synergistic relationship between this genotype and hypertension. In experimental stroke settings estrogens influence recovery of cognitive functions, possibly via induction of neurotrophic factors and specific transcription factors including NGFI-A. This may be related to increased neuroplasticity in the hippocampal formation, a key area for memory processing. Individualized treatment with estrogen receptor ...
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 ...
We have previously demonstrated that endoxifen is the most important tamoxifen metabolite responsible for eliciting the anti-estrogenic effects of this drug in breast cancer cells expressing estrogen receptor-alpha (ERα). However, the relevance of ERβ in mediating endoxifen action has yet to be explored. Here, we characterize the molecular actions of endoxifen in breast cancer cells expressing ERβ and examine its effectiveness as an anti-estrogenic agent in these cell lines. MCF7, Hs578T and U2OS cells were stably transfected with full-length ERβ. ERβ protein stability, dimer formation with ERα and expression of known ER target genes were characterized following endoxifen exposure. The ability of various endoxifen concentrations to block estrogen-induced proliferation of MCF7 parental and ERβ-expressing cells was determined. The global gene expression profiles of these two cell lines was monitored following estrogen and endoxifen exposure and biological pathway analysis of these data sets was
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 ...
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 ...
TY - JOUR. T1 - The changes of estrogen receptor-β variants expression in breast carcinogenesis. T2 - Decrease of estrogen receptor-β2 expression is the key event in breast cancer development. AU - Park, Byeongwoo. AU - Kim, Ki Suk. AU - Heo, Min Kyu. AU - Yang, Woo Ick. AU - Kim, Seung Il. AU - Kim, Joo Hang. AU - Kim, Gwi Eon. AU - Lee, Kyong Sik. PY - 2006/5/1. Y1 - 2006/5/1. N2 - Backgound and Objectives: Although more than five variant forms of estrogen receptor-β (ERβ) have been identilied, their role has not been identified. This study was carried out to investigate the changes of ERβ variants in breast cancer development. Methods: Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERβ variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERβ variants were compared between normal and cancer tissues, and also compared according to various clinicopathological ...
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 ...
Background Assess the relation between the presence of PVUII and XBAI polymorphisms in the estrogen receptor alpha gene and mammographic density in postmenopausal women.. Methods For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADSâ 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized - Adobe Photoshop â 7.0 software). Blood samples were available to extract DNA according to KIT GFX â protocol. PCR-RFLP (Polymerase Chain Reaction - Restriction Fragment Length Polymorphism) was then used to identify the polymorphisms.. Results There was a high degree of agreement among the three readers to determine the mammographic density (Kappa,0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI ...
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. ...
In Silico Prediction of Estrogen Receptor Subtype Binding Affinity and Selectivity Using Statistical Methods and Molecular Docking with 2-Arylnaphthalenes and 2-Arylquinolines. . Biblioteca virtual para leer y descargar libros, documentos, trabajos y tesis universitarias en PDF. Material universiario, documentación y tareas realizadas por universitarios en nuestra biblioteca. Para descargar gratis y para leer online.
There are several potential explanations for the failure of acute hormone replacement therapy to reduce ambulatory ECG ischemia in our study. Although human endothelial cells and smooth muscle cells express estrogen receptors (12,26), Losordo et al. (27)reported that atherosclerotic coronary arteries expressed fewer estrogen receptors than coronary arteries without significant atherosclerosis. Furthermore, Post et al. (28)reported increased rates of estrogen receptor gene promoter methylation with increasing age, both in nondiseased vessels and even more so in areas with atherosclerotic plaque. Increased promoter methylation inactivates estrogen receptor gene transcription. Since women with UA are usually elderly with significant atherosclerosis, they may be unresponsive to hormone therapy due to lack of the estrogen receptor. It also is possible that the concurrent use of nitroglycerin in three-quarters of our patients resulted in maximal endothelial-independent coronary vasodilation, thus ...
Dyslexia, or specific reading disability, is the unexpected failure in learning to read and write when intelligence and senses are normal. One of the susceptibility genes, DYX1C1, has been implicated in neuronal migration, but little is known about its interactions and functions. As DYX1C1 was suggested to interact with the U-box protein CHIP (carboxy terminus of Hsc70-interacting protein), which also participates in the degradation of estrogen receptors alpha (ERalpha) and beta (ERbeta), we hypothesized that the effects of DYX1C1 might be at least in part mediated through the regulation of ERs. ERs have shown to be important in brain development and cognitive functions. Indeed, we show that DYX1C1 interacts with both ERs in the presence of 17beta-estradiol, as determined by co-localization, co-immunoprecipitation and proximity ligation assays. Protein levels of endogenous ERalpha or exogenous ERbeta were reduced upon over-expression of DYX1C1, resulting in decreased transcriptional responses to ...
Estrogen Receptors Inhibitors on signaling pathway are available at Adooq Bioscience. Check Estrogen Receptors pathway , inhibitors reviews and assay information.
TY - JOUR. T1 - Membrane estrogen receptors in GH3/B6 cells are associated with rapid estrogen-induced release of prolactin. AU - Pappas, T. C.. AU - Gametchu, B.. AU - Yannariello-Brown, J.. AU - Collins, T. J.. AU - Watson, C. S.. PY - 1994. Y1 - 1994. UR - UR - M3 - Article. AN - SCOPUS:0028008304. VL - 2. SP - 813. EP - 822. JO - Endocrine. JF - Endocrine. SN - 0969-711X. IS - 9. ER - ...
Epidemiological, clinical and animal studies revealed that sex differences exist in the manifestation and outcome of cardiovascular disease (CVD). The underlying molecular mechanisms implicated in these sex differences are not fully understood. The reasons for sex differences in CVD are definitely multifactorial, but major evidence points to the contribution of sex steroid hormone, 17β-estradiol (E2), and its receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ). In this review, we summarize past and present studies that implicate E2 and ER as important determinants of sexual dimorphism in the physiology and pathophysiology of the heart. In particular, we give an overview of studies aimed to reveal the role of E2 and ER in the physiology of the observed sex differences in CVD using ER knock-out mice. Finally, we discuss recent findings from novel transgenic mouse models, which have provided new information on the sexual dimorphic roles of ER specifically in cardiomyocytes ...
Phosphorylation of estrogen receptor alpha at serine 305 (ER alpha S305-P) by protein kinase A (PKA) or p21-activated kinase 1 (PAK1) has experimentally been associated with tamoxifen sensitivity. Here, we investigated the clinical application of this knowledge to predict tamoxifen resistance in ER-positive breast cancer patients. Using immunohistochemistry, a score including PAK1 and co-expression of PKA and ER alpha S305-P (PKA/ER alpha S305-P) was developed on a training set consisting of 103 patients treated with tamoxifen for metastatic disease, and validated on 231 patients randomized between adjuvant tamoxifen or no treatment. In the training set, PAK1 levels were associated with tumor progression after tamoxifen (HR 1.57, 95% CI 0.99-2.48), as was co-expression of PKA and ER alpha S305-P (HR 2.00, 95% CI 1.14-3.52). In the validation set, a significant tamoxifen benefit was found among the 73% patients negative for PAK1 and PKA/ER alpha S305-P (HR 0.54, 95% CI 0.34-0.87), while others ...
Estrogenic hormones are classically thought to exert their effects by binding to nuclear estrogen receptors and altering target gene transcription, but estrogens can also have nongenomic effects through rapid activation of membrane-initiated kinase cascades. The development of ligands that selectively activate only the nongenomic pathways would provide useful tools to investigate the significance of these pathways. We have prepared large, abiotic, nondegradable poly(amido)amine dendrimer macromolecules that are conjugated to multiple estrogen molecules through chemically robust linkages. Because of their charge and size, these estrogen-dendrimer conjugates (EDCs) remain outside the nucleus. They stimulate ERK, Shc, and Src phosphorylation in MCF-7 breast cancer cells at low concentrations, yet they are very ineffective in stimulating transcription of endogenous estrogen target genes, being approximately 10,000-fold less potent than estradiol in genomic actions. In contrast to estradiol, EDC was ...
Ospemifene D4 (FC-1271a D4) is a deuterium labeled Ospemifene. Ospemifene is a selective and orally active estrogen receptor modulator for the prevention of osteoporosis with IC50 values of 827 nM and 1633 nM for estrogen receptor α (ERα) and ERβ, respectively. Ospemifene has bone-sparing, antitumor, and cholesterol-lowering effects. - Mechanism of Action & Protocol.
Previous microarray studies on breast cancer identified multiple tumour classes, of which the most prominent, named luminal and basal, differ in expression of the oestrogen receptor alpha gene (ER). We report here the identification of a group of breast tumours with increased androgen signalling and a molecular apocrine gene expression profile. Tumour samples from 49 patients with large operable or locally advanced breast cancers were tested on Affymetrix U133A gene expression microarrays. Principal components analysis and hierarchical clustering split the tumours into three groups: basal, luminal and a group we call molecular apocrine. All of the molecular apocrine tumours have strong apocrine features on histological examination (P=0.0002). The molecular apocrine group is androgen receptor (AR) positive and contains all of the ER-negative tumours outside the basal group. Kolmogorov-Smirnov testing indicates that oestrogen signalling is most active in the luminal group, and androgen ...
Aretrospective study comparing the estrogen receptor (ER) alpha subtype and progesterone receptor (PR) profile of breast carcinomas amongst 1625 cases over 2.5 years was carried out. Strictly speaking it is generally believed that breast carcinomas can biochemically express PR only if they are ER-positive. However, a few ERalpha-PR+ cases do exist paradoxically. This class of tumors was the focus of our study in which we looked at the possible reasons for such an immunophenotype and compared it with a group of ERalpha+PR+ breast carcinomas. An internationally recognized immunohistochemical method employing monoclonal antibodies against estrogen and progesterone receptors was used. Correlations with established risk factors i.e. menopausal status, grade, tumor size and lymph node status were analyzed for our study group (ERalpha-PR+) and compared with a control (ERalpha+PR+). Out of the total 1625 cases, 29.91% (486) were ERalpha+PR+, 5.11% (83) were ERalpha+PR-, 56.86% (924) were ERalpha-PR- and 8.12%
The estrogen receptor alpha (ERα) is the central transcriptional regulator of ductal mammary epithelial lineage specification and is an important p...
The vascular consequences of estrogen treatment may be driven by its initiation timing. We tested the hypothesis that the duration of ovarian hormone deprivation before estrogen reintroduction affects the role of estrogen as mediator of endothelial f
SUMMARY, EXPLANATION AND LIMITATIONS:. Recognizes a protein of 67kDa, which is identified as estrogen receptor (ER) alpha. The ER gene consists of more than 140kb of genomic DNA divided into 8 exons, being translated into a protein with six functionally discrete domains, labeled A through F. This antibody strongly stains the nucleus of epithelial cells in breast carcinomas. The ER is an important regulator of growth and differentiation in the mammary gland. Presence of ER in breast tumors indicates an increased likelihood of response to anti-estrogen (e.g. tamoxifen) therapy.. Clone: SP1. Isotype: IgG. Immunogen: Synthetic peptide derived from C-terminal of human estrogen receptor.. Staining pattern: Nuclear.. Positive control: Tissue sample breast carcinoma.. APPLICATIONS:. This antibody is designed for the specific localization of human ER using IHC techniques in formalin-fixed, paraffin-embedded tissue sections.. The antibody identify ER in normal or neoplastic cells and reacts positively ...
Estrogen (E2) is a major risk factor for the initiation and progression of malignancy in estrogen receptor (ER) positive breast cancers, whereas sirtuin 3 (Sirt3), a major mitochondrial NAD+-dependent deacetylase, has the inhibitory effect on the tumorigenic properties of ER positive MCF-7 breast cancer cells. Since it is unclear if this effect is mediated through the estrogen receptor alpha (ERα) signaling pathway, in this study, we aimed to determine if the tumor-suppressive function of Sirt3 in MCF-7 cells interferes with their response to E2. Although we found that Sirt3 improves the antioxidative response and mitochondrial fitness of the MCF-7 cells, it also increases DNA damage along with p53, AIF, and ERα expression. Moreover, Sirt3 desensitizes cells to the proliferative effect of E2, affects p53 by disruption of the ERα–p53 interaction, and decreases proliferation, colony formation, and migration of the cells. Our observations indicate that these tumor-suppressive
in Trabajos del Instituto Cajal (2009), LXXXII. Steroid receptors such as estrogen receptors alpha and beta and androgen receptors are transcription factors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent ... [more ▼]. Steroid receptors such as estrogen receptors alpha and beta and androgen receptors are transcription factors involved in the transcriptional regulation of a large number of target genes. Steroid-dependent expression in the brain controls a large array of biological processes including spatial cognition, copulatory behavior and neuroprotection. The discovery of a competition, or squelching, between two different nuclear receptors introduced the notion that common cofactors might be involved in the modulation of transcriptional activity of nuclear receptors. These cofactors, which are now known as coactivators, are involved in chromatin remodeling and stabilization of the general transcription machinery. Since the characterization of ...
MICHAEL PHELPS: PET molecular imaging probes can rapidly search for cancer throughout all tissues of the body, as well as characterize each cancer lesion it detects within an individual patient. Tumors can change their biological properties as they metastasize, so there is a need to characterize the initial tumor and each metastasis. For example, a patient with breast cancer can first present a tumor in the breast tissue with estrogen receptors, but then develop metastases that may or may not have estrogen receptors. Those metastases with estrogen receptors will likely respond to hormonal therapy, while those without estrogen receptors will not respond. About 40 percent of metastases have a different estrogen receptor status than the primary tumor from which they spread. Whole body PET imaging reveals the estrogen receptors in patients, lesion by lesion, to better determine whether response to hormonal therapy will be effective for all lesions. All cancer treatments are in need of better ...
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ER-alpha and ER-beta function as transcription factors to modulate expression of target genes. Both interact with nuclear regulatory proteins to enhance or inhibit transcription. We hypothesized that these co-regulators are expressed in breast cancer tissue and may be differentially regulated by estrogen and tamoxifen.. ER-alpha, ER-beta, the co-activator SRC-1, and the co-repressor SMRT were localized within breast tissue by immunohistochemistry, and the spatial co-expression assessed by immunofluoresence. The ability of beta-estradiol and 4-hydroxytamoxifen (4-HOT) to modulate the protein of ER-alpha, ER-beta, SRC-1, and SMRT in primary cell cultures, and MCF-7 and T47-D cell lines was assessed by western blotting.. ER-alpha and ER-beta were found to be co-expressed with the co-regulators SRC-1 and SMRT in the nuclei of breast cancer epithelial cells. Partial and complete response elements for the ER were identified on the promotor region of ER-alpha, ER-beta, SRC-1 and SMRT. Beta-estradiol ...
Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression and affect cellular proliferation and differentiation in target tissues. Ligand-dependent nuclear transactivation involves either direct homodimer binding to a palindromic estrogen response element (ERE) sequence or association with other DNA-binding transcription factors, such as AP-1/c-Jun, c-Fos, ATF-2, Sp1 and Sp3, to mediate ERE-independent signaling. Ligand binding induces a conformational change allowing subsequent or combinatorial association with multiprotein coactivator complexes through LXXLL motifs of their respective components. Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF-kappa-B DNA-binding activity and inhibits NF-kappa-B-mediated transcription from the IL6 promoter and displace RELA/p65 and associated coregulators from the promoter. Recruited to the NF-kappa-B response element of
To address globally the issue of tissue specificity of ER ligands, Duke scientists have developed a transgenic mouse that functions as a reporter of ER activity, termed ERIN (estrogen receptor action indicator). ERIN provides a model system that can be used to identify tissues and cells that contain functionally active ER and to define their ability to respond to different ER-ligands. This model system integrates the upstream requirements in ER action (including ER itself, ligand, and accessory comodulators) and results in expression of the enzyme P-galactosidase b-gal) that allows for enzymatic amplification of the signal and histological localization. After a systematic evaluation of seven different estrogen responsive reporters, (3XERE-tk-ZacZ) with the highest absolute level of induction was selected.. ...
This study investigates the molecular mechanisms by which critical genes are differentially regulated in the male and female brain. The hormone, estrogen, is cr...
Your application. Candidates should send a curriculum vitae with a publication list, a short summary of research achievements and mastered techniques, as well as contact information of at least two references to [email protected] Selected publications of the team:. Ando S, Malivindi R, Catalano S, Rizza P, Barone I, Panza S, Rovito D, Emprou C, Bornert JM, Laverny G et al. 2017. Conditional expression of Ki-Ras(G12V) in the mammary epithelium of transgenic mice induces estrogen receptor alpha (ERalpha)-positive adenocarcinoma. Oncogene 36: 6420-6431.. Chambon C, Duteil D, Vignaud A, Ferry A, Messaddeq N, Malivindi R, Kato S, Chambon P, Metzger D. 2010. Myocytic androgen receptor controls the strength but not the mass of limb muscles. Proc Natl Acad Sci U S A 107: 14327-14332.. Duteil D, Chambon C, Ali F, Malivindi R, Zoll J, Kato S, Geny B, Chambon P, Metzger D. 2010. The transcriptional coregulators TIF2 and SRC-1 regulate energy homeostasis by modulating mitochondrial respiration in skeletal ...
To develop novel estrogen receptor (ER) ligands, ring-fused derivatives of the hormonally active (1R,2S)/(1S,2R)-1-(2-chloro-4-hydroxyphenyl)-2-(2,6-dichloro-4-hydroxyphenyl)ethylenediamine 4b were synthesized. (2R,3S)/(2S,3R)-2-(2-Chloro-4-hydroxyphenyl)-3-(2,6-dichloro-4-hydroxyphenyl)piperazine 4 induced ligand-dependent gene expression in MCF-7-2a cells, stably transfected with the plasmid ERE(wtc)luc and was therefore used as a lead structure. The influence of the substitution pattern in the aromatic rings (4-OH (1), 2-F,4-OH (2), 2-Cl,4-OH (3), 2,6-Cl2,3-OH (5), and 2,6-Cl2,4-OH (6)) and the effect of N-ethyl chains on the ER binding and activation of gene expression were studied. The synthesis started from the respective methoxy-substituted (1R,2S)/(1S,2R)-configurated 1,2-diarylethylenediamines 6b to 4b, which were reacted with dimethyl oxalate in order to get 5,6-diarylpiperazine-2,3-diones. Reduction with BH3*tetrahydrofuran and ether cleavage with BBr3 yielded the piperazines 1-6. The N
Figure 3 Thermogenic program and β3-adrenergic receptor signaling is mediated by membrane-initiated ERα signaling. A: Immunoblot analysis of UCP1 levels in BAT and pWAT of ERα+/+, ERα−/−, WT, and KRRki/ki mice. Representative immunoblots and quantification are shown (n = 5-8 per group). #P , 0.01. B: qRT-PCR analysis of genes consistent with beige adipocytes in adipose tissues of ERα+/+, ERα−/−, WT, and KRRki/ki mice (n = 6-8). Relative mRNA expression levels are normalized to gapdh. *P , 0.05, #P , 0.01. C: Hematoxylin and eosin staining of pWAT of ERα+/+, ERα−/−, WT, and KRRki/ki mice. Scale bar indicates 100 µm. The graph depicts the quantification of mean cell area (n = 4). #P , 0.01. D: qRT-PCR analysis of genes consistent with beige adipocytes in NIH 3T3-L1 preadipocytes treated with vehicle (control), 100 nmol/L E2, or 2 µmol/L rosiglitazone for 72 h. Relative mRNA expression levels are normalized to gapdh. Data depict the results from three independent experiments. ...
Berkeley Lab researchers have developed the first clinically-relevant mouse model of human breast cancer to successfully express functional estrogen receptor positive adenocarcinomas. This model should be a powerful tool for testing therapies for aggressive ER+ breast cancers and for studying luminal cancers -- the most prevalent and deadliest forms of breast cancer.
Trial finds estrogen receptor degrader significantly increases progression-free survival in patients with advanced breast cancer.
Communications DOI: 10.1002/anie.201101655 DNA Complexes DNA-Controlled Bivalent Presentation of Ligands for the Estrogen Receptor** Frank Abendroth, Alexander Bujotzek, Min Shan, Rainer Haag, Marcus Weber, and Oliver Seitz* The assembly of DNA complexes proceeds according to known rules. Thus, the mutual recognition of DNA conjugates can be used for the precise positioning of functional groups. For example, chromophores,[1] metals,[2] catalytic units,[3] nanoparticles,[4] fluorophores[5] and even proteins[6] have been arranged at well-defined distances by means of DNA hybridization. Until recently, the main interest was focused on issues within materials science as well as on the immobilization of biomolecules. We and others assumed that the ability to position functional units at defined distances could also be used to address biological problems.[7] According to this, DNA may serve as a molecular ruler to determine the distance between binding pockets in biological receptors. Due to ...
mouse anti-estrogen receptor alpha, ligand binding domain (aa 304-554) hybridoma (ERalpha BZ1) is an eagle-i resource of type Hybridoma cell line at eagle-i Network Shared Resource Repository.
First estrogen eeceptor-α mutation identified in a young woman. A receptor mutation that essentially blocks estrogens action has been identified in a female.
Researchers then monitored the response of estrogen receptor-alpha (ERa) - the bodys main bone-related mediator of the hormone - to the estradiol. In particular, the group wanted to know whether the inhibition of one of the ERas two activation functions, known as AF-1 and AF-2, would redirect estrogen to specific tissues ...
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Estrogen Receptor Alpha Ligand Binding Domain in Complex with Lasofoxifene ... Estrogen Receptor Alpha Ligand Binding Domain in Complex with Lasofoxifene. *PDB DOI: 10.2210/pdb6VJD/pdb ... Estrogen receptor. A, B, C, D. 249. Homo sapiens. Mutation(s): 3 Gene Names: ESR1, ESR, NR3A1. ...
The objective of this study was to elucidate mechanisms of improved effectiveness of combined targeting of ER&alpha; and the ... This finding demonstrated that combined targeting of XPO1 and ER&alpha; rewired the metabolic pathways and shut down both ... Using the Seahorse metabolic profiler, we showed that ER&alpha;-XPO1 targeting changed the metabolic phenotype of TAM-resistant ... There is a critical need for novel therapeutic approaches to resensitize recurrent ER&alpha; (+) tumors to endocrine therapies ...
Selective mutations in estrogen receptor alpha D-domain alters nuclear translocation and non-estrogen response element gene ... Estrogen receptor-alpha mediates the protective effects of estrogen against vascular injury. Circulation research. 2002;90:1087 ... Estrogen receptor alpha is a major mediator of 17beta-estradiols atheroprotective effects on lesion size in Apoe-/- mice. The ... Activation of estrogen receptor-alpha protects the in vivo rabbit heart from ischemia-reperfusion injury. American journal of ...
Clark, S., Pollard, K., Rainville, J. and Vasudevan, N. (2015) Detection of the phosphorylation of the estrogen receptor alpha ... Detection of the phosphorylation of the estrogen receptor alpha as an outcome of GPR30 activation ... In particular, phosphorylation of the ERα is one possible outcome of activation of the putative membrane estrogen receptor (mER ... Phosphorylation of the serine residues in estrogen receptor (ER) α is important in transcriptional activation. Hence, methods ...
The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains ... The androgen receptor (AR) plays a central role in establishing an oncogenic cascade that drives prostate cancer progression. ... The oestrogen receptor alpha (ERα) is expressed in prostate cancers, independent of AR status. However, the role of ERα remains ... The oestrogen receptor alpha-regulated lncRNA NEAT1 is a critical modulator of prostate cancer ...
... and in estrogen receptor alpha (ERα)-negative and ERα-positive breast tumors. Relevant genes were further investigated in a ... Breast cancer growth is regulated by estrogen, which acts by binding to its estrogen receptor alpha (ERα). The presence of ERα ... Table 5 Relationships between mRNA values of the seven selected genes and the ERα gene in the 97 estrogen receptor alpha (ERα)- ... Table 4 mRNA levels of seven selected genes in 97 estrogen receptor alpha-positive breast tumors. Full size table. ...
Adam, AHB, de Haan, LHJ, Estruch, IM, Hooiveld, GJEJ, Louisse, J & Rietjens, IMCM 2020, Estrogen receptor alpha (ERα)-mediated ... title = "Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist ... T1 - Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist ... Estrogen receptor alpha (ERα)-mediated coregulator binding and gene expression discriminates the toxic ERα agonist ...
In human breast cancer, the overall duration of estrogen exposure is the most important risk factor for developing estrogen- ... Accordingly, it has been suggested that estrogen exposure reduces apoptosis through the up-regulation of the anti-apoptosis ... Furthermore, treatment with 17β-estradiol (E2) stimulated growth and up-regulated Bcl-2 expression in estrogen responsive ... Wang, LS., Huang, YW., Liu, S. et al. Conjugated linoleic acid induces apoptosis through estrogen receptor alpha in human ...
... α and androgen receptor (AR) degradations via the ubiquitin-proteasome system (UPS) were developed. The designated inducers ... Estrogen Receptor alpha / chemistry * Estrogen Receptor alpha / metabolism* * Humans * MCF-7 Cells ... Peptide-based inducers of estrogen receptor (ER) α and androgen receptor (AR) degradations via the ubiquitin-proteasome system ... Design and synthesis of peptide-based chimeric molecules to induce degradation of the estrogen and androgen receptors Bioorg ...
One of the most important mediators of estrogenic action is the estrogen receptor alpha. We have investigated whether ... Estrogen receptor alpha gene polymorphism and endometrial cancer risk : a case-control study. Permanent link. https://hdl. ... polymorphic variation in the estrogen receptor alpha gene (ESR1) is associated with endometrial cancer risk. Methods: In 702 ... Background: Estrogen is an established endometrial carcinogen. ...
... nuclear receptors, pten, e-cadherin, raf, tgfbeta, tsc2, mtorc1, egfr, her2, pelp1, rap1, foxo3a, camkiv, il-6, notch, mlck, ... p120, rad51, pras40, b-raf, smad3, plc, dapk, alpha-catenin, smad2, crk, zyxin, pa125, survivin, snail, nrg, acinus, rac, pkd, ... Estrogen receptor alpha signaling pathways tagged: signaling, pi3k, p53, p38, ras, beta-catenin, stat3, apoptosis, jnk, pdk1, ... Estrogen receptor alpha signaling pathways.,bound method SlideThumb.key of ,model. ...
Home › Estrogen receptor alpha Antibody, Biotin Conjugated Estrogen receptor alpha Antibody, Biotin Conjugated. ... ER; ESR; Era; ESRA; ESTRR; NR3A1; Estrogen receptor; ER-alpha; Estradiol receptor; Nuclear receptor subfamily 3 group A member ... Mutual transrepression occurs between the estrogen receptor (ER) and NF-kappa-B in a cell-type specific manner. Decreases NF- ... Nuclear hormone receptor. The steroid hormones and their receptors are involved in the regulation of eukaryotic gene expression ...
... an increasing body of evidence has linked estrogen receptor beta (ERß) to prostate cancer, the function of estrogen receptor ... Here, we show that prostate cancer cells express ER? and estrogen induces oncogenic properties in prostate cancer cells through ... in cancer cells suggesting that estrogen/ER? signaling promotes crosstalk between cancer and osteoblastic progenitors to ... alpha (ER?) in prostate cancer is not very well studied. We have discovered a novel role of ER? in the pathogenesis of prostate ...
By competing against estrogen with various selective estrogen receptor modulators (SERMs) and estrogen receptor agonists and ... One endometrial protein that fluctuates in response to progesterone is the estrogen receptor-alpha (ER alpha), being down- ... changes might be effectively treated by timely administration of the appropriate anti-estrogens to artificially block ER alpha ... we hypothesize that certain types of uterine receptivity defects may be caused by the loss of appropriate ER alpha down- ...
Tekmal, RR, Liu, YG, Nair, HB, Jones, J, Perla, RP, Lubahn, DB, Korach, KS & Kirma, N 2005, Estrogen receptor alpha is ... title = "Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic ... T1 - Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic ... Estrogen receptor alpha is required for mammary development and the induction of mammary hyperplasia and epigenetic alterations ...
Aromatase deficiency is a condition characterized by reduced levels of the female sex hormone estrogen and increased levels of ... Aromatase and estrogen receptor alpha deficiency. Fertil Steril. 2014 Feb;101(2):323-9. doi: 10.1016/j.fertnstert.2013.12.022. ... In females, estrogen guides female sexual development before birth and during puberty. In both males and females, estrogen ... As a result, there is a decrease in estrogen production and an increase in the levels of androgens, including testosterone. In ...
Background: This study aims to assess the expression of estrogen receptor alpha (ERα), progesterone receptor A (PRA),Her-2-neu ... Expression of Immunohistochemical Markers Estrogen Receptor Alpha, Progesterone Receptor A, Her2-neu, p53, and Ki-67 in ... Expression of Immunohistochemical Markers Estrogen Receptor Alpha, Progesterone Receptor A, Her2-neu, p53, and Ki-67 in ... Tumors with adverse prognostic factors express ERα and PRA; this supports the mitogenicrole of estrogen and estrogenic ...
Order Estrogen Receptor-alpha Phospho-Ser104 antibody Blocking peptide sequence 01010452229 at Gentaur Estrogen Recepr alpha ... Description: The Estrogen Receptor-alpha (Phospho-Ser104) antibody Blocking peptide sequence is a α- or alpha protein sometimes ... When such chemical-signals couple or bind to a receptor, they cause some form of cellular/tissue-response, e.g. a change in the ... The High-efficiency solid phase peptide synthesis (HE-SPPS) is give very low production costs.The receptors are ligand binding ...
Estrogen Receptor-alpha (ER) drives 75% of breast cancers. Stimulation of the ER by estra-2-diol forms a transcriptionally- ... Humans, Estradiol, Neoplasm Proteins, Estrogen Receptor alpha, Signal Transduction, Gene Expression Regulation, Neoplastic, ... Holding, A. N., Cullen, A. E., & Markowetz, F. (2018). Genome-wide Estrogen Receptor-α activation is sustained, not cyclical.. ... Binding Sites, Base Sequence, Protein Binding, Genome, Human, Female, Receptors, CXCR, Promoter Regions, Genetic, Genome-Wide ...
Antibodies directed against the estrogen receptor alpha (ERα) revealed dark (type 1) and light (type 2) nuclear positive ... Antibodies directed against the estrogen receptor alpha (ERα) revealed dark (type 1) and light (type 2) nuclear positive ... Antibodies directed against the estrogen receptor alpha (ERα) revealed dark (type 1) and light (type 2) nuclear positive ... Antibodies directed against the estrogen receptor alpha (ERα) revealed dark (type 1) and light (type 2) nuclear positive ...
Estrogen receptor-alpha is developmentally regulated during osteoblast differentiation and contributes to selective ... We examined the expression of estrogen receptor-alpha (ER) messenger RNA (mRNA) in cultured rat calvarial-derived osteoblasts ... Receptors, Estrogen. Time Factors. Transforming Growth Factor beta. Up-Regulation. Cell Biology Show allShow less ... Estrogen responsiveness of bone is a fundamental regulatory mechanism operative in skeletal homeostasis. ...
METHODS AND RESULTS: We detected an estrogen receptor alpha (ERalpha) transcript in human endothelial cells that encodes a ... However, estrogen-stimulated transcriptional activation mediated by Delta1a-hERalpha-46 was much less than with ERalpha-66. ... Both ERalpha isoforms colocalized with eNOS and mediated acute activation of eNOS in response to estrogen stimulation. ... the identity of the receptors involved in this rapid response remains unclear. ...
Will Rickes lab, for being awarded a NIEHS R01 supplemental grant to study estrogen receptor alpha in relation to the ... Will Rickes lab, awarded a NIEHS R01 supplement to study estrogen receptor alpha in relation to the development of LUTD ... Will Rickes lab, awarded a NIEHS R01 supplement to study estrogen receptor alpha in relation to the development of LUTD. ... Will Rickes lab, for being awarded a NIEHS R01 supplemental grant to study estrogen receptor alpha in relation to the ...
Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic activation of ... abstract = "Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic ... N2 - Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic ... AB - Estrogen causes nitric oxide (NO)-dependent vasodilation due to estrogen receptor (ER) alpha-mediated, nongenomic ...
Jia M, Dahlman-Wright K and Gustafsson JA: Estrogen receptor alpha and beta in health and disease. Best Pract Res Clin ... All phthalates activated the estrogen receptor in vitro.. Figure 3. ER transcription factor assay. Activation of estrogen ... Paterni I, Granchi C, Katzenellenbogen JA and Minutolo F: Estrogen receptors alpha (ERα) and beta (ERβ): Subtype-selective ... mediated by nuclear receptors such as the estrogen receptor (ER) (17,18). ERs exist in 2 isoforms: ERα (ESR1) and ERβ (ESR2), ...
Allred DC, Brown P, Medina D. The origins of estrogen receptor alpha-positive and estrogen receptor alpha-negative human breast ... of breast cancers are Estrogen Receptor alpha (ER-α) positive and are dependent on estrogen for growth. Selective estrogen ... 4],[5] The biological effects of estrogens are mediated by estrogen receptor alpha (ER-α), a member of the superfamily of ... Introduction of estrogen receptor-alpha into the tTA / TAg conditional mouse model precipitates the development of estrogen- ...
So, I imprint both epitope (for example: epitope for estrogen alpha receptor) and anti-cancer drug simultaneously to achieve ... Nowadays, I am synthesizing novel molecular imprinted polymeric nanoparticles (nanoMIPs) for the estrogen positive breast ...

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