Estrogen receptor alpha. Medical search

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)

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. ...

https://www.rcsb.org/structure/6VJD

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 ...

https://www.mdpi.com/2072-6694/11/4/479

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 ...

https://www.medsci.org/v10p0457.htm

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 ...

https://centaur.reading.ac.uk/58940/

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 ...

https://ckbiobank.kairuku.haiku.fry-it.com/publications/1242269

... 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. ...

https://breast-cancer-research.biomedcentral.com/articles/10.1186/bcr784

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 ...

https://research.wur.nl/en/publications/estrogen-receptor-alpha-er%CE%B1mediated-coregulator-binding-and-gene-

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 ...

https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-8-208

... 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 ...

https://pubmed.ncbi.nlm.nih.gov/32631565/

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. ...

https://munin.uit.no/handle/10037/2146

... 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. https://www.scienceslides.com/thumb/,bound method SlideThumb.key of ,model. ...

https://scienceslides.com/g3v/estrogen-receptor-alpha-signaling-pathways

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 ...

https://www.biossusa.com/products/bs-0253r-biotin

... 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 ...

https://www.omicsdi.org/dataset/biostudies/S-EPMC4792564

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- ...

https://rbej.biomedcentral.com/articles/10.1186/1477-7827-4-S1-S9

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 ...

https://scholars.uthscsa.edu/en/publications/estrogen-receptor-alpha-is-required-for-mammary-development-and-t

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 ...

https://medlineplus.gov/genetics/condition/aromatase-deficiency/

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 ...

https://imsear.searo.who.int/handle/123456789/209153

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 ...

https://blockinganti.com/product-catalogs/12553-genways/12663-estrogen-receptor-alpha-phospho-ser104-antibody-blocking-peptide-sequence

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 ...

https://www.repository.cam.ac.uk/handle/1810/287052

GDC-9545 IN COMPLEX WITH ESTROGEN RECEPTOR ALPHA - 7MSA , canSARS ... GDC-9545 IN COMPLEX WITH ESTROGEN RECEPTOR ALPHA EXPRESSION ...

https://corona-1.cansar.icr.ac.uk/structure/7MSA/3d/7MSA_A

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 ...

https://asu.pure.elsevier.com/en/publications/estrogen-receptor-immunoreactivity-within-subregions-of-the-rat-f

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. ...

https://repository.escholarship.umassmed.edu/handle/20.500.14038/49642

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. ...

https://www.cardioscience.ox.ac.uk/publications/104210

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 ...

https://obrien.urology.wisc.edu/2021/04/09/dr-debra-garvey-post-doc-in-dr-will-rickes-lab-awarded-a-niehs-r01-supplement-to-study-estrogen-receptor-alpha-in-relation-to-the-development-of-lutd/

... a Covalent Antagonist of Estrogen Receptor Alpha, in Women With Locally Advanced or Metastatic Estrogen Receptor-positive, HER2 ...

https://thestormriders.org/clinical_trial/nct03250676-trial-of-h3b-6545-a-covalent-antagonist-of-estrogen-receptor-alpha-in-women-with-locally-advanced-or-metastatic-estrogen-receptor-positive-her2-negative-breast-cancer/

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 ...

https://utsouthwestern.pure.elsevier.com/en/publications/estrogen-receptor-alpha-and-endothelial-nitric-oxide-synthase-are

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), ...

https://www.spandidos-publications.com/10.3892/wasj.2021.92?text=fulltext

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- ...

http://carcinogenesis.com/article/2037/mouse-models-of-estrogen-receptor-positive-breast-cancer-2

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 ...

https://www.ncl.ac.uk/engineering/staff/profile/pankajsingla.html

Anatomy28

Organisms9

Diseases10

Chemicals and Drugs124

Analytical, Diagnostic and Therapeutic Techniques and Equipment32

Phenomena and Processes54

Disciplines and Occupations1

Information Science3

Health Care1

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)

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

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

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

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

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

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

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

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Estrogen Receptor alpha

Receptors, Estrogen

Estrogen Receptor beta

Estrogens

Estradiol

Selective Estrogen Receptor Modulators

Breast Neoplasms

Estrogen Antagonists

Estrogen Receptor Modulators

Tamoxifen

Receptors, Progesterone

Ovariectomy

Uterus

Cell Line, Tumor

Estrogens, Non-Steroidal

Response Elements

Phytoestrogens

RNA, Messenger

Transcription, Genetic

Estrogens, Conjugated (USP)

Transcriptional Activation

Ligands

Aromatase

Signal Transduction

Gene Expression Regulation

Promoter Regions, Genetic

Raloxifene

Gene Expression Regulation, Neoplastic

Protein Binding

Immunohistochemistry

Antineoplastic Agents, Hormonal

Transcription Factors

Reverse Transcriptase Polymerase Chain Reaction

Nuclear Receptor Coactivator 1

Diethylstilbestrol

Nuclear Receptor Coactivator 2

Transfection

Estradiol Congeners

Neoplasms, Hormone-Dependent

MCF-7 Cells

Tumor Cells, Cultured

Phenols

Blotting, Western

Base Sequence

Cell Proliferation

Molecular Sequence Data

Binding Sites

PPAR alpha

Mice, Knockout

Receptors, Androgen

Receptors, Cytoplasmic and Nuclear

Receptor Cross-Talk

Interleukin-13 Receptor alpha2 Subunit

Methoxychlor

Ethinyl Estradiol

Gene Expression

Mice, Inbred C57BL

Nuclear Receptor Coactivator 3

Benzhydryl Compounds

Nuclear Receptor Coactivators

Retinoid X Receptor alpha

Estrogens, Catechol

Endocrine Disruptors

Interleukin-13 Receptor alpha1 Subunit

Cell Nucleus

Dose-Response Relationship, Drug

Cells, Cultured

Chromatin Immunoprecipitation

Estrous Cycle

Protein Structure, Tertiary

Postmenopause

Phosphorylation

Cell Line

Receptors, Retinoic Acid

Rats, Sprague-Dawley

Progesterone

Genes, Reporter

COS Cells

Thyroid Hormone Receptors alpha

Receptor, erbB-2