Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.1.26.9 (ribonuclease)
6,589 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We generate pure estrogen receptor protein in Xenopus oocytes by injecting them with estrogen receptor mRNA synthesized in vitro. A chromosomal vitellogenin gene, which normally responds to estrogen only in liver cells, is activated. Primer extension shows that initiation is accurate, and ribonuclease mapping shows that the first exon is correctly spliced out of the initial transcript. Long transcripts are produced, one being equal in length to poly(A)- vitellogenin mRNA. Immunochemical estimates of receptor levels in the oocyte nuclei suggest that pure receptor, acting alone, cannot activate oocyte vitellogenin genes unless unusually large amounts are present. However, when a receptor-free extract from liver cells is also injected, the amount of receptor required is reduced. Such an extract, but not pure receptor, can also activate albumin genes in oocytes.
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PMID:Activation of chromosomal vitellogenin genes in Xenopus oocytes by pure estrogen receptor and independent activation of albumin genes. 224 78

Much clinical evidence indicates that androgens have beneficial effects in the treatment of breast cancer in women. Physiological concentrations of androgens strongly inhibit both basal and estrogen-induced cell proliferation in the human breast cancer cell line ZR-75-1 through their interaction with the androgen receptor. The present study shows that androgens strongly suppress estrogen receptor (ER) and progesterone receptor contents in this model, as measured by radioligand binding and anti-ER monoclonal antibodies. Similar inhibitory effects are observed on the levels of ER messenger RNA (mRNA) measured by ribonuclease protection assay. The androgenic effect is observed at subnanomolar concentrations of the nonaromatizable androgen 5 alpha-dihydrotestosterone, regardless of the presence of estrogens, and is competitively reversed by the antiandrogen hydroxyflutamide. Such data on ER expression provide an explanation for at least part of the antiestrogenic effects of androgens on breast cancer cell growth and moreover suggest that the specific inhibitory effects of androgen therapy could be additive to the standard treatment limited to blockade of estrogens by antiestrogens.
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PMID:Down-regulation of estrogen receptors by androgens in the ZR-75-1 human breast cancer cell line. 266 Dec 9

Rat uterine and anterior pituitary microsomes each contain a population of specific estrogen-binding sites. Saturation binding of estradiol is demonstrable, with an affinity similar to that of the cytosol estrogen receptor (Ka = 1-2 X 10(10) M-1). Dissociation rate kinetic determinations, however, revealed that estrogen-microsomal complexes are 4 times as stable as cytosol estrogen-receptor complexes. Sedimentation properties in sucrose gradients were salt-dependent, yielding values of 10S in KCl-free buffer and 5.5S in the presence of 0.4 M KCl. The concentration of microsomal sites varies in proportion to the level of cytosol estrogen receptor, such that microsomal binding constitutes a consistent 20% of the total extranuclear binding capacity. Binding is sensitive to pronase, but not to ribonuclease or deoxyribonuclease; steroidal specificity differs from cytosol receptor only with respect to a greater extent of competition by progesterone. Microsomal binding sites are readily extractable with KCl-free hypotonic buffer or with 0.4 M KCl, but are resistant to extraction by 0.15 M KCl. The presence of estradiol lends stability to the microsomal binding sites, while high salt has a deleterious effect on their longevity. After exhaustive extraction of binding sites, microsomes are capable of accepting cytosol estradiol-receptor complexes to a level corresponding to the concentration of depleted binding sites; microsomes from nontarget tissue do not manifest such capability. However, the original microsomal estrogen-binding sites are not simply cytosol receptor contaminants, as evidenced by the observations that the microsomal binding site concentration is independent of the volume of tissue homogenate (indicating that a trapping phenomenon is not operative) and that nonextracted microsomes are not potential acceptor sites for cytosol estradiol-receptor complexes. In considering total cellular dynamics of estrogen and estrogen receptor turnover, it thus becomes important to explore the role of the microsomal compartment, since it functions as a repository of specific estrogen-binding sites and may have significant acceptor capability for the cytosol estrogen-receptor complex.
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PMID:Specific binding of estrogen and estrogen-receptor complex by microsomes from estrogen-responsive tissues of the rat. 402 80

The largest and smallest discrete forms of the estrogen receptor in human breast tumor cytosol were characterized by competitive steroid binding, ultracentrifugation, gel filtration, and electrophoresis in polyacrylamide gels of several concentrations. Incubation of cytosol with [3H]estradiol and centrifugation in glycerol gradients containing 20 mM Na2MoO4 and 0 or 150 mM KCl revealed a 9-10S form of the receptor. It resembles the molybdate-stabilized complexes in cytosols of other human and rodent, malignant and healthy tissues, and the complex detected in breast tumor cytosol containing leupeptin, a bacterial protease inhibitor. Preservation of receptor integrity during purification and discrimination from serum steroid-binding components are facilitated by inclusion of molybdate in all buffers. Possible mechanisms of action of molybdate include the inhibition of ribonuclease action on RNA-associated receptor forms and protection against specific proteolytic cleavage by stabilization of a phosphate group on the vulnerable residue or a neighboring one. During fractionation of tumor cytosol in the absence of molybdate, the receptor is converted to a mixture of fragments. The smallest that retains the bound steroid, the mero-receptor, resembles the products of endogenous and exogenous protease action on receptors for all classes of steroids in a wide range of tissues. The similarities between both the largest and the smallest known forms of the breast tumor estrogen receptor and corresponding forms of other receptors support the notion of the common architecture of steroid receptors in normal and malignant tissues of diverse origins.
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PMID:Human breast tumor estrogen receptor: effects of molybdate and electrophoretic analyses. 747 73

Forty-one human pituitary adenoma specimens were examined for the presence of estrogen receptor (ER) messenger ribonucleic acid and protein using a combination of ribonuclease protection assay, [3H] estradiol ([3H]E2) binding, and ER immunohistochemistry. ER messenger ribonucleic acid prevalence was high in PRL-immunoreactive tumors (2 of 2), moderate in GH/PRL tumors (2 of 5), and low or absent (0 of 4) in GH tumors. In the GH/PRL-immunostaining tumors, the presence of the ER was uniformly associated with elevated serum PRL levels. Among the gonadotropin-immunostaining tumors, 10 of 17 were ER positive; within this group, those with gonadotroph adenoma characteristics were ER positive, whereas those with null cell/oncocytic characteristics were ER negative. Of the tumors that did not immunostain for any known anterior pituitary hormones, 3 of 11 were ER positive. ER immunohistochemistry in 14 tumors revealed a 100% correlation with ribonuclease protection assay results, whereas [3H]E2 binding, determined in 9 tumors, showed an 87% correlation. In summary, it appears that PRL and a specific class of gonadotropin-immunostaining tumors (identifiable by specific characteristics on electron microscope) contain ER, whereas GH-immunostaining tumors are ER negative. ER expression in normal pituitary paralleled that in macroadenomas (GH, 2.3%; PRL, 50%; FSH, 70%; LH, 83%; TSH, 4%; ACTH, 1%). The ER-positive tumors represent a subset whose growth and secretory profiles may be influenced by the gonadal steroidal milieu or by pharmacological agents that affect E2 levels or ER function.
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PMID:Estrogen receptor expression in human pituitary: correlation with immunohistochemistry in normal tissue, and immunohistochemistry and morphology in macroadenomas. 751 90

1,25(OH)2-Vitamin D3 inhibits breast cancer cell proliferation through interaction with the vitamin D receptor (VDR). Regulation of VDR is under the influence of several factors which include the functional ligand for this receptor (1,25(OH)2-vitamin D3) as well as heterologous steroid hormones. We evaluated the nature of homologous regulation in T-47D human breast cancer cells with a radiolabelled ligand binding assay and a ribonuclease protection assay for VDR. Significant VDR up-regulation, as measured by hormone binding assays, occurred with pre-incubations with 10(-9)M through 10(-6)M 1,25(OH)2-vitamin D3 (P < 0.05). A 7-fold VDR up-regulation with 10(-8)M 1,25(OH)2-vitamin D3 occurred at 4 h treatment and was not associated with an increase in VDR mRNA expression on ribonuclease protection assay. This supports the hypothesis that up-regulation of VDR is probably the result of ligand-induced stabilization of pre-existing receptor. All-trans-retinoic acid, the progesterone analog R-5020, and prednisone were found to induce heterologous up-regulation of the VDR. We then determined with ligand binding assays whether 1,25(OH)2-vitamin D3 could influence receptor levels for another hormone in a manner analogous to the heterologous regulation of VDR. Regulation of estrogen receptor (ER) by 1,25(OH)2-vitamin D3 was studied in T-47D and MDA-MB-231 breast cancer cells. Incubation of T-47D cells, which are ER (+), with 10(-8)M 1,25(OH)2-vitamin D3 did not result in up-regulation of ER. Yet estrogen binding was significantly up-regulated in a cell line that is ER(-), MDA-MB-231. The increased estrogen binding was associated with a shift in binding affinity and ribonuclease protection assay showed absence of ER mRNA in these cells, suggesting an up-regulation of estrogen binding proteins and not of the ER itself.
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PMID:Modulation of vitamin D receptor and estrogen receptor by 1,25(OH)2-vitamin D3 in T-47D human breast cancer cells. 766 88

Recently a family of six distinct insulin-like growth factor binding proteins (IGFBPs) have been identified and the gene structures of the first five (IGFBP-1, -2, -3, -4 and -5) characterized. We now isolated the IGFBP-6 gene from a rat genomic library and determined its organization as well as the DNA sequence at the 5' flanking region of the gene. The rat IGFBP-6 gene spans 5.1 kb of the genomic sequence and contains four exons interrupted by three introns of approximately 2.4, 0.2 and 1.2 kb in length, respectively. Primer extension analysis and ribonuclease protection assay using RNA from rat lung tissues demonstrated two transcriptional start sites located at 85 and 82 nucleotides upstream of the ATG translational initiation codon. The promoter region of the rat IGFBP-6 gene is devoid of a TATA or a CAAT consensus sequence motif, but putative regulatory cis elements, including a Sp1, an estrogen receptor binding site and a retinoic acid responsive element, are present in the promoter region.
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PMID:Structural characterization of the rat insulin-like growth factor binding protein-6 gene. 768 65

The insulin-like growth factors (IGFs) have been implicated in the growth regulation of human breast cancer. Since the IGFs are associated with specific binding proteins (IGFBPs) which may modulate receptor/ligand interactions, production of IGFBPs by breast cancer cells could alter their IGF-dependent growth. This study examined the expression of IGFBPs 4, 5, and 6 in eight breast cancer cell lines (BCCLs) using ribonuclease (RNase) protection assays. IGFBP-4 mRNA was detected in all BCCLs studied. IGFBP-5 expression was higher in estrogen receptor (ER) positive cells, while IGFBP-6 mRNA was detected in only two ER negative BCCLs. We also found that E2 treatment enhanced the expression of IGFBPs 2, 4, and 5 in T47-D cells. We next studied IGFBP mRNA expression in 40 primary breast tumors. All tumors expressed mRNA for IGFBPs 2-6 but none expressed IGFBP-1 message. IGFBP-3 expression was higher in ER negative tumors, while that of IGFBP-4 and -5 was higher in ER positive specimens. These differences were statistically significant (P < .05). Ligand blot analysis of tumor extracts confirmed the presence of IGFBPs in breast cancer tissues. Thus, differential IGFBP expression in ER positive and negative tumors suggests an important role for this protein in breast cancer biology.
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PMID:Expression of insulin-like growth factor binding proteins in human breast cancer correlates with estrogen receptor status. 769 42

A 5.2-kb mRNA band that contains estrogen receptor (ER) sequence and exhibits sex- and tissue-specific expression has been identified in rat pituitary via Northern analysis; this band is composed of at least two distinctive ER mRNA isoforms. This mRNA is expressed in high levels in female pituitary but is absent in male pituitary and uterus, whereas the mRNA encoding the full-length receptor (6.2 kb) is expressed in all the aforementioned tissues. Estradiol treatment potently induces the expression of the 5.2-kb band in the male pituitary. Oligonucleotide hybridization and ribonuclease-protection experiments indicate that the pituitary ER variant is missing exons 1-4. Two corresponding cDNA clones, truncated estrogen receptor product 1 and 2 (TERP-1 and TERP-2), were isolated by using the anchored PCR. Both sequences contain a 31-bp segment of specific sequence upstream of exon 5; TERP-2, however, contains an additional 66 bp of specific sequence between the 31-bp segment and exon 5. On Northern analysis, probes complementary to the 31-bp segment of specific sequence hybridize only to the 5.2-kb band. Immunoblotting identified several proteins in rat pituitary that could represent the translation products of these or related transcripts. In summary, several ER isoforms have been identified that exhibit both tissue-specific expression and marked estrogen regulation and differ from full-length receptor by virtue of sequence upstream of the exon 4/5 boundary. Physiologically, the putative proteins encoded by these or similar isoforms might be important modulators of the tissue- and promoter-specific effects of estradiol.
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PMID:Estrogen regulates the expression of several different estrogen receptor mRNA isoforms in rat pituitary. 775 13

We have recently shown that oxytocin (OT) is synthesized within human amnion, chorion, and decidua during late gestation. The levels of OT messenger ribonucleic acid (mRNA) increased around the time of parturition, suggesting that locally produced OT may play a role in this poorly understood process. In this report, we present results from investigations into the effects of estrogen and progesterone on the synthesis of OT by human chorio-decidua. Using an in vitro incubation system, estradiol at physiological concentrations more than doubled the concentration of OT mRNA. This was reflected by an increase in the amount of OT peptide secreted into the medium. The increase in OT mRNA was antagonized by tamoxifen, suggesting that the effects were estrogen receptor mediated. Progesterone had no effect on OT mRNA synthesis. Using ribonuclease protection assays, mRNAs for estrogen receptor (ER) and progesterone receptor (PR) were detected in all tissues examined. The highest levels were found in decidua, with lower amounts in chorion and very small amounts in amnion and placenta. This is the same relative tissue distribution that we previously demonstrated for OT mRNA. A single transcript was present for ER, and two transcripts were protected for PR. The concentrations of ER mRNA in chorio-decidua were 3-fold higher in tissues obtained after spontaneous labor onset than in tissues obtained from cesarean section at a similar gestational age but before labor onset. Levels of PR did not change significantly. We conclude that synthesis of OT in human chorio-decidua may be regulated in part by estrogen, and that regulation of ER levels may be an important factor modulating this effect. These data support the hypothesis of a paracrine network within human fetal membranes and decidua that may participate in regulating the timing of human birth.
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PMID:Estrogen stimulates oxytocin gene expression in human chorio-decidua. 785 22


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