Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.1 (RNase)
 16,360 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An antigen was detected in pooled human nephroblastomas using antiserum prepared in rabbits against an ethylemediaminetetra acetic acid (EDTA) extract of the tumors. This antigen was not found in normal human plasma or kidney extracts, and was not related to the ABO or Forssman blood groups. The antigen was detected in extracts of cultured nephroblastoma cells, but was not present in extracts of normal human fetal kidney cell cultures. The antigen is believed to be present at the cell surface, as cell viability was not significantly lowered during the extraction procedure. A reaction of complete identity was demonstrated by Ouchterlony double diffusion experiments with this antigen and purified bovine fetuin. The antigen was not found in extracts of human fetal spleen, thymus or kidney, nor in human fetal serum. Furthermore, the antigen does not possess determinants in common with the human alpha-fetoprotein of hepatomas, nor was it detected in human renal clear cell carcinoma. Initial characterization of the antigen showed it to be nondialysable, not sedimentable at 100,000 times g for 2 h, stable to repeated freeze-thawing and to incubation at 56 degrees C for 1 h, and water soluble over a wide pH range. The antigen was susceptible to digestion with pronase and trypsin and possibly hyaluronidase, but not to ribonuclease or neuraminidase. The protein portion is therefore of major importance to the structural integrity of this antigen. The relationship between this antigen and other abnormal materials reported previously in nephroblastoma patients is being studied.
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PMID:A fetuin-like antigen from human nephroblastoma. 5 Feb 93

The cloning and molecular characterization of two putative tumor genes, WT1 and WIT1, from the chromosome 11p13 region has provided a means of evaluating their role in the generation of Wilms' tumor heterogeneity. A series of 29 tumors were analyzed for WT1 and WIT1 expression by Northern blot or RNase protection analyses, and results were compared with tumor histopathology. Tumors were scored for the percentage of mesenchymal and epithelial derived tissue components. Homotypic tumors comprised blastema, tubular epithelium, and a fibroblast-like mesenchyme. In addition to these tissue components, the group of tumors designated as heterotypic also contained ectopic cell phenotypes such as muscle and squamous epithelium. The analyses suggest that heterotypic differentiation patterns occur when WT1 and WIT1 expression is low relative to normal fetal kidney. In situ hybridization using antisense RNA probes showed that WT1 and WIT1 were concordantly expressed in normal fetal kidney and in the blastema of tumors. The ratio of WT1:WIT1 expression remained relatively constant in homotypic tumors but deviated significantly in heterotypic tumors. These results suggest that expression patterns of the WT1 and WIT1 genes can be closely correlated to Wilms' tumor histopathology.
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PMID:Coordinate expression of Wilms' tumor genes correlates with Wilms' tumor phenotypes. 133 80

The chromosome 11p13 Wilms tumor susceptibility gene WT1 appears to play a crucial role in regulating the proliferation and differentiation of nephroblasts and gonadal tissue. The WT1 gene consists of 10 exons, encoding a complex pattern of mRNA species: four distinct transcripts are expressed, reflecting the presence or absence of two alternative splices. Splice I consists of a separate exon, encoding 17 amino acids, which is inserted between the proline-rich amino terminus and the zinc finger domains. Splice II arises from the use of an alternative 5' splice junction and results in the insertion of 3 amino acids between zinc fingers 3 and 4. RNase protection analysis demonstrates that the most prevalent splice variant in both human and mouse is that which contains both alternative splices, whereas the least common is the transcript missing both splices. The relative distribution of splice variants is highly conserved between normal fetal kidney tissue and Wilms tumors that have intact WT1 transcripts. The ratio of these different WT1 mRNA species is also maintained as a function of development in the mouse kidney and in various mouse tissues expressing WT1. The conservation in structure and relative levels of each of the four WT1 mRNA species suggests that each encoded polypeptide makes a significant contribution to normal gene function. The control of cellular proliferation and differentiation exerted by the WT1 gene products may involve interactions between four polypeptides with distinct targets and functions.
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PMID:Alternative splicing and genomic structure of the Wilms tumor gene WT1. 165 87

The Wilms tumor locus on chromosome 11p13 has been mapped to a region defined by overlapping, tumor-specific deletions. Complementary DNA clones representing transcripts of 2.5 (WIT-1) and 3.5 kb (WIT-2) mapping to this region were isolated from a kidney complementary DNA library. Expression of WIT-1 and WIT-2 was restricted to kidney and spleen. RNase protection revealed divergent transcription of WIT-1 and WIT-2, originating from a DNA region of less than 600 bp. Both transcripts were present at high concentrations in fetal kidney and at much reduced amounts in 5-year-old and adult kidneys. Eleven of 12 Wilms tumors classified as histopathologically heterogeneous exhibited absent or reduced expression of WIT-2, whereas only 4 of 14 histopathologically homogeneous tumors showed reduced expression. These data demonstrate a molecular basis for the pathogenetic heterogeneity in Wilms tumorigenesis.
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PMID:Tissue, developmental, and tumor-specific expression of divergent transcripts in Wilms tumor. 217 45

Chloride channels supply critical functions in epithelial cells throughout the body. Although function of the volume- and voltage-gated C1C-2 is uncertain, its wide tissue distribution of mRNA suggests C1C-2 has important housekeeping functions. This study's objective was to identify the extent of not only C1C-2 mRNA expression but also protein expression as a measure of the capacity for C1C-2 chloride secretion in epithelial tissues. Using quantitative ribonuclease protection assay, we found that C1C-2 mRNA transcripts were abundant in fetal and postnatal brain, fetal kidney, liver, intestine, and lung. In contrast to brain, C1C-2 mRNA transcripts were downregulated during late gestation in lung, kidney, and intestine. The lung expressed the least C1C-2 mRNA. Immunoblotting demonstrated similar tissue- and gestation-dependent variations in C1C-2 protein expression. To determine if there is a correlation between the sites of C1C-2 protein expression and cystic fibrosis transmembrane conductance regulator (CFTR), another epithelial chloride channel, a polyclonal COOH-terminal C1C-2 antibody and an anti-R domain CFTR anti-body were used. C1C-2 and CFTR were expressed in different sites in lung and kidney.
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PMID:Gestational and tissue-specific regulation of C1C-2 chloride channel expression. 894 27

We have previously shown that the p57KIP2 gene, which encodes a cyclin-dependent kinase inhibitor, undergoes genomic imprinting and lies within a 700-kb domain of imprinted genes on 11p15, including IGF2 and H19. Loss of heterozygosity and loss of imprinting (LOI) of this region are frequently observed in Wilms' tumor (WT) and other embryonal malignancies. Although LOI of p57KIP2 was observed in some WTs (approximately 10%), allele-specific expression was preserved in most tumors examined. Because our initial studies were inconclusive concerning the absolute expression level of p57KIP2 in WT, we developed a sensitive and quantitative RNase protection assay to determine if changes in p57KIP2 expression play a role in WT. Expression of p57KIP2 was found to be virtually absent in 21 of 21 WTs compared to matched normal kidney from the same patients, as well as compared to fetal kidney. We also examined p57KIP2 expression in the normal kidney and tongue of patients with Beckwith-Wiedemann syndrome (BWS), which predisposes to WT and also involves LOI of IGF2 and H19. Although p57KIP2 was undetectable in BWS tongue, similar results were also observed in postnatal non-BWS tongue samples. Most primary skin fibroblast cultures of BWS cell lines exhibited normal imprinting of p57KIP2. However, one BWS patient did show LOI of p57KIP2 in skin fibroblasts. Thus, p57KIP2 is part of a domain of genes on 11p15 that show altered expression and, in some cases, altered imprinting in WT and BWS.
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PMID:Reduced expression of the cyclin-dependent kinase inhibitor gene p57KIP2 in Wilms' tumor. 897 Nov 82

Wilms' tumor, or nephroblastoma, arises from metanephric blastema and caricatures renal organogenesis. An alteration in at least one of the genes involved in control of renal differentiation is therefore a likely event in tumorigenesis, and indeed some of the genes involved in renal development, for example, hepatocyte growth factor (HGF) and its receptor c-met, the transcription factor Wilms' tumor gene (WT1), and transforming growth factor-beta family member bone morphogenetic protein (BMP)-7, have also been implicated in various models of tumorigenesis. In a comparison of mRNA expression patterns for these genes in normal rat embryonic or fetal kidney and nephroblastoma, we found that the patterns for HGF, met, and WT1 detected by in situ hybridization or ribonuclease protection assay (RPA) in the nephroblastomas were similar to those of normal developing kidney. BMP-7 expression, on the other hand, was lower in most tumors examined both by in situ hybridization and RPA than in normal tissues. This deficiency in a defined inductive factor that has been shown to function in renal tubulogenesis may play a role in tumorigenesis by allowing the accumulation of blastemal populations typical of nephroblastomas.
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PMID:Deficient expression of mRNA for the putative inductive factor bone morphogenetic protein-7 in chemically initiated rat nephroblastomas. 980 58

During kidney organogenesis, the Na+-K+-ATPase pump is not restricted to the basolateral plasma membrane of the renal epithelial cell but is instead either localized to the apical and lateral membrane sites of the early nephron or expressed in a nonpolarized distribution in the newly formed collecting ducts. The importance of Na+-K+-ATPase beta-subunit expression in the translocation of the Na+-K+-ATPase to the plasma membrane raises the question as to which beta-subunit isoform is expressed during kidney organogenesis. Immunocytochemical, Western analysis and RNase protection studies showed that both beta2-subunit protein and beta2 mRNA are expressed in the early gestation to midgestation human metanephric kidney. In contrast, although beta1 mRNA abundance is equivalent to that of the beta2-subunit in the metanephric kidney, the beta1-subunit protein was not detected in early to midgestation metanephric kidney samples. Immunocytochemical analysis revealed that both alpha1- and beta2-subunits were present in the apical epithelial plasma membranes of distal nephron segments of early stage nephrons, maturing loops of Henle, and collecting ducts during kidney development. We also detected a significant increase in alpha1 and beta1 mRNA after birth with a marked reduction in beta2 mRNA abundance associated with an increase in alpha1- and beta1-subunit proteins and loss of beta2 protein expression. These studies support the conclusion that the expression of the beta2-subunit in the fetal kidney may be an important mechanism controlling polarization of the Na+-K+-ATPase pump in the epithelia of the developing nephron during kidney organogenesis.
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PMID:Expression of the beta2-subunit and apical localization of Na+-K+-ATPase in metanephric kidney. 1048 23

Renal and cardiovascular responses to an intravenous infusion of ANG II (1 microg/h) or saline for 3 days were examined in ovine fetuses at midgestation (75-85 days of gestation, term 150 days). ANG II caused an increase in fetal blood pressure (36 +/- 2 to 44 +/- 3 mmHg) and urine flow rate (8 +/- 2 to a maximum of 18 +/- 6 ml/h). Plasma renin concentrations decreased in ANG II-infused fetuses. Fetal fluids (amniotic and allantoic) did not differ in volume or composition between the groups when measured at postmortem. There was no difference in the expression levels of the mRNA for the angiotensin (AT(1) or AT(2)) receptors between the two groups when measured by an RNase protection assay. However, there was a significant decline in renin and AT(1) receptor gene expression when measured by a real-time polymerase chain reaction method. These results indicate that ANG II is diuretic and pressor when infused at midgestation. ANG II can feedback to decrease renin secretion by the fetal kidney, and this may occur by decreased renin gene expression.
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PMID:Angiotensin II infusion to the midgestation ovine fetus: effects on the fetal kidney. 1100 95