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)

Pheochromocytomas occur sporadically or in individuals affected by inherited syndromes including multiple endocrine neoplasia (MEN) type 2A and 2B, neurofibromatosis, and the von Hippel-Lindau syndrome (vHL). Medullary thyroid carcinomas (MTCs) also occur sporadically or as part of MEN 2A, MEN 2B, and familial MTC. Little is known of the molecular genetic background of these tumors. We have shown previously that activation of the N-ras, H-ras, and K-ras oncogenes does not occur in these tumors, but that deletions of the short arm of chromosome 1 are extremely common (> 60%) and may indicate loss of a suppressor gene in the chromosomal region 1p31-36. We have examined the structure and expression of N-myc, c-myc, L-myc, c-mos, nerve growth factor (beta-NGF), and the low affinity nerve growth factor receptor (LNGFR) in a series of pheochromocytomas and MTCs from patients with hereditary and sporadic diseases. Southern analysis, using radiolabeled DNA probes, revealed no evidence of amplification or rearrangement of these genes in any normal or tumor tissues except for loss of heterozygosity at the L-myc locus (1p32) in 9 pheochromocytomas from patients with MEN 2A or MEN 2B, in 5 of 11 non-MEN pheochromocytomas, and in 3 of 24 non-MEN MTCs. Gene expression at the RNA level was examined by Northern analysis or ribonuclease protection assay (RPA) using radiolabeled DNA or cRNA probes. C-myc transcripts were detectable at low levels in all tumors tested.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Oncogene and growth factor expression in MEN 2 and related tumors. 136 25

The stabilities of different mRNA species were analyzed in a reticulocyte lysate system under protein-synthesizing conditions. In all cases examined the relative mRNA degradation by reticulocyte ribonucleases as well as by the interferon-modulated (2'-5') (A)n-dependent endonuclease correlated with the extent of (U)nA sequences within the 3' non-coding region. The experimental data presented indicate that according to their stabilities at least three major mRNA groups may be identified: (a) (U)nA-poor mRNAs (e.g. globin) are essentially stable and are only slightly degraded by the (2'-5')(A)n-dependent endonuclease; (b) mRNA species with intermediate (U)nA levels (e.g. Ig alpha and Ig mu heavy-chain mRNAs) are partially degraded by general ribonuclease activity and further degraded by the (2'-5')(A)n-dependent endonuclease and (c) (U)nA-rich mRNA species (such as c-myc and non-skeletal actin mRNAs) are inherently unstable and are extremely sensitive to degradation by general ribonuclease activity. A survey of mRNA nucleotide sequences demonstrated that without exception (U)nA-rich stretches appeared more frequently within the 3' non-coding region than in the coding or 5' non-coding regions. A comparison of 3' non-coding region sequences from 92 different mRNAs revealed that transiently expressed mRNAs, such as the interleukins, nerve growth factor, epidermal growth factor receptor, c-myc, c-fos, c-myb and several other oncogenes as well as interferons alpha, beta and gamma were exceptionally (U)nA-rich. It is postulated that differential mRNA stability may be partly determined by the primary nucleotide sequence and in particular by (U)nA sequences within the 3' non-coding region. This may represent a novel post-transcriptional strategy employed by the cell to selectively retain or destroy discrete mRNA species.
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PMID:Differential mRNA stability to reticulocyte ribonucleases correlates with 3' non-coding (U)nA sequences. 335

The possible roles of certain oncogenes in the development of pituitary tumors has not been investigated. We have examined the expression of c-myc, c-fos, and c-myb in a number of human pituitary tumors by ribonuclease protection assays, as these oncogenes have been implicated to have roles in the pathogenesis of other human tumors (12, 13, 15, 16). In several tumors examined (9 of 30) c-myc was expressed at levels 4-9 times greater than the level detected in normal postmortem pituitary. Although a larger percentage of negative immunohistochemical-staining tumors overexpressed c-myc, c-myc over-expression was not limited to this group of tumors. c-Fos was overexpressed in 1 of 30 tumors examined at a level 5.8-fold higher than that detected in normal postmortem pituitary. This tumor stained positive for ACTH by immunohistochemistry and was considered highly aggressive, demonstrating invasion beyond the sella turcica; however, when other ACTH-staining and invasive pituitary tumors were examined, no abnormality in the expression of c-fos was detected. In 30 tumors, c-myb was expressed at approximately the same level as that detected in normal postmortem pituitary. We conclude that c-myc is overexpressed in a subgroup of pituitary tumors and that this overexpression occurs broadly among the different groups of immunohistochemical-staining tumors. c-Fos overexpression appears to be much less common in pituitary tumors and does not necessarily correlate with the ability of the tumor to become invasive. c-Myb does not appear to have a role in the pathogenesis of pituitary tumors.
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PMID:c-myc, c-fos, and c-myb gene expression in human pituitary adenomas. 802 38

Epidemiology suggests a possible relationship between exposure to power frequency magnetic fields (EMF) and breast cancer. One mechanism through which EMF could stimulate breast cancer induction is via altered expression of oncogenes and/or tumor suppressor genes that regulate normal and neoplastic growth. To evaluate the hypothesis that EMF action in the breast is mediated by alterations in gene expression, transcript levels of c-myc and a battery of other cancer-associated genes were quantitated in human breast epithelial cells exposed to pure, linearly polarized 60 Hz EMF with low harmonic distortion. HBL-100 cells and normal (non-transformed) human mammary epithelial cells were exposed to EMF flux densities of 0.1, 1.0 and 10.0 Gauss (G) for periods ranging from 20 min to 24 h; concurrent sham controls were exposed to ambient fields (<0.001 G) only. Gene expression was quantitated using ribonuclease protection assays. EMF exposure had no statistically significant effect on basal levels of c-myc transcripts in either human breast cell model, and had no effect on alterations in c-myc expression induced by 12-O-tetradecanoylphorbol-13-acetate. Transcript levels of c-erbB-2, p53, p21, GADD45, bax, bcl-x, mcl-1, and c-fos were also unaffected by EMF exposure. These results suggest that EMF is unlikely to influence breast cancer induction through a mechanism involving altered expression of these genes.
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PMID:Gene expression in human breast epithelial cells exposed to 60 Hz magnetic fields. 1042 19

Proto-oncogenes are involved in the regulation of gene expression, for example after ligand binding to growth factor receptors. Expression of the proto-oncogenes c-fos, c-jun, c-ha-ras and c-myc was studied in in vivo grown and in vitro cultured bovine preimplantation blastocysts employing RT-PCR, ribonuclease protection assay and immunohistochemistry. Thirteen- and 14- day-old preimplantation blastocysts, i.e. stages before and during trophoblast elongation, were used. In in vivo-grown blastocysts c-fos, c-jun and c-ha-ras transcripts as well as c-Fos, c-Jun and c-Myc proteins were detected in all stages studied. Cultured blastocysts were treated with 10 nM epidermal growth factor and 10 nM transforming growth factor-alpha simultaneously. Epidermal growth factor and transforming growth factor-alpha treatment induced c-fos mRNA and c-Myc protein expression. The induction of downstream targets of the epidermal growth factor receptor by epidermal growth factor and transforming growth factor-alpha indicates a functional epidermal growth factor signal transduction pathway in elongating bovine blastocysts.
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PMID:Expression of proto-oncogenes in bovine preimplantation blastocysts. 1083 31

Previous work from this laboratory identified a polysome-associated endonuclease whose activation by estrogen correlates with the coordinate destabilization of serum protein mRNAs. This enzyme, named polysomal ribonuclease 1, or PMR-1, is a novel member of the peroxidase gene family. A characteristic feature of PMR-1 is its ability to generate in vitro degradation intermediates by cleaving within overlapping APyrUGA elements in the 5'-coding region of albumin mRNA. The current study sought to determine whether the in vivo destabilization of albumin mRNA following estrogen administration involves the generation of decay intermediates that could be identified as products of PMR-1 cleavage. A sensitive ligation-mediated polymerase chain reaction technique was developed to identify labile decay intermediates, and its validity in identifying PMR-1-generated decay intermediates of albumin mRNA was confirmed by primer extension experiments performed with liver RNA that was isolated from estrogen-treated frogs or digested in vitro with the purified endonuclease. Ligation-mediated polymerase chain reaction was also used to identify decay intermediates from the 3'-end of albumin mRNA, and as a final proof of principle it was employed to identify in vivo decay intermediates of the c-myc coding region instability determinant corresponding to sites of in vitro cleavage by a polysome-associated endonuclease.
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PMID:Identification of in vivo mRNA decay intermediates corresponding to sites of in vitro cleavage by polysomal ribonuclease 1. 1115 74

Zinc-alpha(2)-glycoprotein (Znalpha(2)gp) is widely distributed in body fluids and epithelia. Its expression in stratified epithelia increases with differentiation. We previously showed that Zn alpha(2)gp has ribonuclease activity, and that squamous tumor cells grown on a matrix of Znalpha(2)gp were growth-inhibited. Here we demonstrate, both by adding Znalpha(2)gp to the culture medium and, more unequivocally, by stably transfecting SiHa cells with Znalpha(2)gp cDNA, that the introduction of Znalpha(2)gp into SiHa tumor cells reduces proliferation. In response to Znalpha(2)gp, we find an accumulation of the cell population in G(2)/M by flow cytometry, paralleling the reduction of proliferation. In order to distinguish growth inhibition by cell cycle arrest from that produced by apoptosis or differentiation, we examine by RT-PCR how Znalpha(2)gp affects the expression of genes commonly used as markers of these properties. No changes are observed for PCNA, p53, c-myc, or bcl-2. Only cdc2 expression responds to Znalpha(2)gp, with a reduction of up to over a factor of two. Cdc2 is the only cyclin-dependent kinase regulating the G(2)/M transition without redundancy and is required as a rate-limiting step in the cell cycle. Its increased expression has been directly linked to increased proliferation and decreased differentiation of advanced tumors; conversely, its downregulation by Znalpha(2)gp might hinder tumor progression. J. Cell. Biochem. Suppl. 36: 162-169, 2001.
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PMID:Zinc-alpha(2)-glycoprotein hinders cell proliferation and reduces cdc2 expression. 1145 81

Antioxidants have been proposed as a promising treatment for restenosis after percutaneous transluminal coronary angioplasty (PTCA), but their mechanism of action remains unclear. Here, we investigated the effect of antioxidants on gene expression in the artery after balloon denudation. We developed a sensitive ribonuclease (RNase) protection assay for the messenger RNA (mRNA) levels of immediate early (IE) genes (c-jun, c-fos and c-myc), as well as platelet-derived growth factor-A (PDGF-A), platelet-derived growth factor-beta receptor, transforming growth factor-beta 1, and vascular endothelial growth factor. New Zealand White rabbits were fed a 0.17% cholesterol diet containing vehicle, BO-653 or probucol, and balloon denudation for iliac arteries was performed. The iliac arteries were then removed at 4 h after the denudation, for IE genes, and 10 days after for growth factors and receptors. Both BO-653 and probucol significantly reduced neointimal thickening, compared with the control. In terms of gene expression, BO-653, but not probucol, significantly inhibited c-myc induction. On the other hand, probucol, but not BO-653, significantly inhibited PDGF-A expression. Neither treatment had any effect on the expression of other genes. These results suggest that antioxidants affect the gene expression of the neointimal response and that both BO-653 and probucol inhibit gene expression in specific manners.
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PMID:Effect of BO-653 and probucol on c-MYC and PDGF-A messenger RNA of the iliac artery after balloon denudation in cholesterol-fed rabbits. 1188 18

The Myc family of genes regulates proliferation, differentiation, and apoptosis. Temporal expression of Myc family genes and several pro-apoptotic genes were investigated during Swiss Webster mice organogenesis after maternal treatment with an oral dose of 100 mg/kg trans-retinoic acid (RA) or vehicle on day 10 post-coitum. Reverse transcriptase-polymerase chain reaction and ribonuclease protection assay revealed decreased c-myc expression at 48 h followed by an increase at 72 h in fetuses from RA-treated dams. Increased c-Myc protein was detected at 72 h in the RA-treated group. In utero RA-treatment resulted in decreased expression of max, mad, caspases, bax, and bad genes at 48 h. Terminal uridinetriphosphate nick end-labeling (TUNEL) analysis revealed increased apoptosis at 24-48 h, followed by decreased apoptosis 72 h after in utero RA-exposure, which correlated with the decreased expression of pro-apoptotic genes noted at 48 h. Further investigations are needed to understand the role of Myc family genes during RA-mediated teratogenesis.
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PMID:Expression of c-Myc and other apoptosis-related genes in Swiss Webster mouse fetuses after maternal exposure to all trans-retinoic acid. 1212 97

Fumonisin B1 (FB1), a mycotoxin, is a potent inhibitor of ceramide synthase, and produces organ-, species-, and even gender-specific toxic responses in animals. The hepatotoxic response of FB1 in mice involves accumulation of free sphingoid bases and induction of inflammatory cytokines including tumor necrosis factor alpha (TNFalpha). The FB1-induced hepatotoxic responses were reduced in mice lacking TNFalpha receptor (TNFR) 1 or TNFR2. However, the hepatotoxicity was exacerbated in mice lacking TNFalpha. We therefore investigated the modulation of various other apoptotic signaling factors in TNFalpha-knockout (TKO) mice compared to wild-type (WT) strain after repeated daily subcutaneous injections of 2.25 mg/kg FB1 treatment for 5 days. Expression of various signaling genes in liver was evaluated by ribonuclease protection assay. Expression of CD95-ligand (FasL) was more than doubled in TKO animals after FB1 whereas it was unaltered in the WT group. FB1 did not alter CD95 expression in either strain; however, expressions of TRAIL, and downstream signaling factors FADD, TRADD, and caspase 8 were higher in FB1-treated TKO mice than in the corresponding WT animals. The TKO strain had a higher constitutive expression of apoptotic factors except CD95L. In addition to the CD95 and TNFalpha systems, the expression of apoptotic molecules bcl-2, b-myc, c-myc, bax, max, mad and IL1alpha was induced by FB1 in TKO mice to a greater extent than in WT animals; many of these factors also had a higher constitutive expression in TKO animals than WT mice. Results indicated that FB1 can induce CD95 modulated signaling when TNFalpha is absent. Differential constitutive expression of apoptotic genes in TKO mice may explain their increased sensitivity to FB1. These results are important in characterizing the modulating effect of TNFalpha on apoptotic signaling and in explaining the unexpected sensitivity of mice lacking this cytokine in response to hepatotoxic xenobiotics.
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PMID:Increased expression of CD95-ligand and other apoptotic signaling factors by fumonisin B1, a hepatotoxic mycotoxin, in livers of mice lacking tumor necrosis factor alpha. 1459 19


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