Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Wnt gene expression was investigated by ribonuclease protection analysis in human breast cancer, nontumorous breast tissue, and a variety of human breast cell lines. We report the expression of Wnt3, Wnt4, and Wnt7b in human breast cell lines and Wnt2, Wnt3, Wnt4, and Wnt7b in human breast tissues. Wnt3a and Wnt7a were absent in the cell lines and tissues tested. The level of expression of Wnt2 and Wnt4 was 10- to 20-fold higher in fibroadenomas than it was in normal or malignant breast tissue, and in 10% of tumors Wnt7b expression was 30-fold higher than in normal or benign breast tissues. In contrast to the mouse, in which Wnt1 and Wnt3 are involved in tumorigenesis, our results suggest that Wnt2, Wnt4, and Wnt7b may be associated with abnormal proliferation in human breast tissue.
Cancer Res 1994 May 15
PMID:Differential expression of human Wnt genes 2, 3, 4, and 7B in human breast cell lines and normal and disease states of human breast tissue. 816 88

The goal of this work was to study the effect of the most common Egyptian food items, Vicia faba beans (VF) and bran, on the carcinogenicity of dibutylnitrosamine (DBN) precursors (dibutylamine and nitrite). Mice receiving DBN precursors showed a delayed gain in body weight as well as decreased protein level and 5-nucleotidase activity. Acid ribonuclease, alkaline phosphatase, and DNA level and rate of synthesis were significantly increased compared with corresponding controls. Hepatomas and bladder papillomas developed in 60% and 40% of mice, respectively, after nine months of treatment. On the other hand, administration of VF or bran, in addition to DBN precursors, lessened the damage caused by DBN precursors alone, except DNA level and rate of synthesis were elevated. Alkaline phosphatase was also elevated when bran was administered with DBN precursors. However, these elevations were still less than corresponding elevations in mice receiving DBN precursors alone. The incidence of hepatoma was also reduced to only 20% for both groups. Meanwhile, incidence of bladder papillomas was only 20% in mice receiving VF in addition to DBN precursors, and bladder papillomas were completely absent in mice receiving bran in addition to DBN precursors. In vitro studies were also performed to clarify the effect of VF or bran on diphenylnitrosamine (DPhNA) and its formation from its precursors (diphenylamine and nitrite). The study revealed that VF and bran have the ability to eliminate nitrite and DPhNA from the reaction media and to reduce the rate of formation of DPhNA from its precursors. This reaction depends on the concentration and form of VF or bran and the duration of the reaction. Thus it is concluded that some naturally occurring food items, such as VF and bran, could protect humans against the hazardous effect of nitrosamines and their precursors.
Nutr Cancer 1994
PMID:Effect of Vicia faba and bran feeding on nitrosamine carcinogenesis and formation. 818 23

Recent evidence suggests that the expression of estrogen receptor (ER) variants in breast cancer may interfere with wild-type (wt) ER function and be related to tumor progression and resistance to hormone treatment. One of these variants, ER delta E5, lacking that part of the hormone-binding domain encoded by exon 5, has previously been identified in breast tumors with the unusual estrogen receptor negative (ER-) and progesterone receptor positive (PgR+) phenotype and found to possess constitutive and hormone-independent transcriptional activity. Using a ribonuclease protection assay, we analyzed 27 breast tumors and 4 breast cell lines for the presence of this variant. We found the ER delta E5 variant to be expressed, not only in all of three ER-/PgR+ tumors but also in 19 of 20 ER+/PgR+ or ER+/PgR- tumors. Moreover, the variant was always coexpressed with and often in excess of wtER. ER delta E5 was also found in three breast cancer cell lines (MCF7, T47D, and ZR75-1), although to a lesser extent than wtER. A complete absence of both ER delta E5 and wtER was noted in four ER-/PgR- tumors and one normal breast cell line (HBL-100). Thus, our data suggest that the occurrence of ER delta E5 in breast cancer may represent a critical stage in tumor progression to autonomy.
Cancer Res 1993 Dec 15
PMID:An exon 5 deletion variant of the estrogen receptor frequently coexpressed with wild-type estrogen receptor in human breast cancer. 826 97

Annexin II is a substrate for oncogene and growth factor-associated protein-tyrosine kinases. Elevated expression of annexin II is seen in different types of cancers and recent evidence indicates a role for annexin II in DNA synthesis and cell proliferation. In this report we show that the level of annexin II is subject to cell cycle regulation. Chinese hamster ovary cells were selected without the use of drugs, by the mitotic cell selection technique. As the mitotic cells progressed synchronously through the cell cycle, we determined the steady-state levels of annexin II mRNA and protein. The half-life of annexin II mRNA was approximately 2 h as measured by pulse-chase and ribonuclease protection analyses. Steady-state levels of both annexin II mRNA and protein were high in mitotic cells. As the cells divided and entered G1, there was a reduction in the levels of both annexin II mRNA and protein. New synthesis of annexin II mRNA and protein occurred in early G1 and maximal expression of annexin II mRNA and protein occurred as the cells entered S-phase. A gradual reduction in steady-state levels of annexin II mRNA and protein occurred as cells progressed through S-phase. Similar results were obtained in HeLa cells. In HeLa cells, collected at various cell cycle stages by countercurrent centrifugal elutriation, we observed peak expression of annexin II in G1-S and S-G2 cells. We conclude from our results that annexin II expression is regulated during the mammalian cell cycle.
Cancer Res 1993 Dec 15
PMID:Annexin II expression is regulated during mammalian cell cycle. 826 16

The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I-CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to--but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed.
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PMID:The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas. 835 95

In independently derived drug-resistant sublines of the mouse lymphoid tumor P388, multidrug resistance is associated with the exclusive overexpression of the mdr3 gene. In P388/VCR cells, mdr3 overexpression occurs in the absence of gene amplification, while in P388/ADM-2 cells overexpression is associated with mdr3 gene amplification. The mechanism underlying mdr3 overexpression in these cells was investigated. Measurement of the rate of transcription by nuclear "run-on" assays showed that increased mdr3 expression in P388/VCR cells was caused by transcriptional activation of the gene. Analysis of the 5' end of mdr3 mRNA transcripts by primer extension indicated that in P388/VCR cells, these mRNAs extended approximately 200 nucleotides upstream exon 2, about 60 nucleotides longer than their counterparts expressed in normal tissues from the known transcription start site of the gene (TS1). Northern blotting experiments using discrete exon and intron probes derived from the 5' end of the gene near TS1, together with ribonuclease protection using a complementary RNA probe from the same region, demonstrated that transcriptional activation in P388/VCR cells occurred from a novel transcription start site named TS3, located either upstream of TS1 or within intron 1 at a site immediately upstream a novel exon. In P388/ADM-2 cells, Northern blotting and ribonuclease protection identified overexpressed mdr3 mRNAs initiating near TS1 and a large partially spliced mdr3 mRNA species initiating upstream of TS1 at a novel initiation site designated TS2. Therefore, mdr3 overexpression in independently derived multidrug-resistant isolates of P388 cells is associated with the appearance of novel transcription start sites in the gene and novel sequences at the 5' end of the overexpressed mRNAs.
Cancer Res 1993 Apr 01
PMID:Transcriptional activation of the mouse mdr3 gene coincides with the appearance of novel transcription initiation sites in multidrug-resistant P388 tumor cells. 845 38

Urinary gonadotrophin peptide (UGP) was originally identified by immunoassay in the urine of patients with various types of cancer and by immunohistochemistry in human cancers of various histological types. Extracts of normal adult male urine also contained UGP by immunoassay. Purified UGP from different starting material was subjected to high pressure liquid chromatography (HPLC) prior to defining amino acid sequences. Chromatographed UGP after HPLC showed three distinct fractions. The N-terminal sequence of peptide 2 was completely homologous with the beta-core fragment of human chorionic gonadotrophin (hCG) and this was found associated with two smaller peptides. The N-terminal sequence of peptide 1 has not been described previously whilst the N-terminus of peptide 3 that was sequenced showed complete homology with the N-terminal sequence of eosinophil derived neurotoxin and non-secretory ribonuclease. The monoclonal antibodies 2C2 and 6D3 only bind beta core-fragment (peptide 2) whilst the polyclonal (rabbit) antibody AK12 could bind all three peptides. The radioimmunoassay system using AK12 could be inhibited by all three peptides and the immunoradiometric assay although based on a capture antibody (2C2) that only bound peptide 2, had the potential to measure all three peptides (when bound together as UGP) at the second step when 125I-AK12 was introduced as the detector. A specific radioimmunoassay for peptide 3 was generated using 125I-peptide 3 and the AK12 antibody. Beta core-fragment on iso-electric focusing was found to have a pI > 9.5, peptide 3 showed two bands at pI = 3.5 and 3.8 whilst insufficient purified peptide 1 was available to determine its iso-electric point. Bioassay studies on UGP showed that any biological activity could be attributed to trace contamination with hCG.
Br J Cancer 1993 Apr
PMID:Characterisation of UGP and its relationship with beta-core fragment. 847 26

Tumour angiogenesis is a complex multistep process regulated by a number of angiogenic factors. One such factor, platelet-derived endothelial cell growth factor has recently been shown to be thymidine phosphorylase (TP). TP catalyses the reversible phosphorylation of thymidine to deoxyribose-1-phosphate and thymine. Although known to be generally elevated in tumours, the expression of this enzyme in breast carcinomas is unknown. Therefore, we used ribonuclease protection assays and immunohistochemistry to examine the expression of TP in 240 primary breast carcinomas. Nuclear and/or cytoplasmic TP expression was observed in the neoplastic tumour epithelium in 53% of tumours. Immunoreactivity was also often present in the stromal, inflammatory and endothelial cell elements. Although endothelial cell staining was usually focal, immunoreactivity was observed in 61% of tumours and was prominent at the tumour periphery, an area where tumour angiogenesis is most active. Tumour cell TP expression was significantly inversely correlated with grade (P = 0.05) and size (P = 0.003) but no association was observed with other tumour variables. These findings suggest that TP is important for remodelling the existing vasculature early in tumour development, consistent with its chemotactic non-mitogenic properties, and that additional angiogenic factors are more important for other angiogenic processes like endothelial cell proliferation. Relapse-free survival was higher in node-positive patients with elevated TP (P = 0.05) but not in other patient groups. This might be due to the potentiation of chemotherapeutic agents like methotrexate by TP. Therefore, this enzyme might be a prediction marker for response to chemotherapy.
Br J Cancer 1996 Feb
PMID:The angiogenic factor platelet-derived endothelial cell growth factor/thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. 856 30

Considerable remodeling of the extracellular matrix as well as cellular migration takes place during embryogenesis. Since the metalloproteinase MMP-9 is implicated in these functions in cancer cells, we studied the patterns of expression of MMP-9 mRNA during the development of post-implantation mouse embryos. MMP-9 mRNA was detected using the ribonuclease protection assay in poly A+RNA from 13 to 17 day embryos, but not at 11 days. In order to localize these transcripts, in situ hybridization was performed on sections of murine embryos from 7.5 to 15 days of gestation. At the time of implantation, MMP-9 mRNA was localized to the invading trophoblast cells. Strong signals were also seen in the yolk sac. No signal for MMP-9 mRNA was seen by in situ hybridization in the embryo until day 11 when detectable reaction was seen in the central nervous system. By day 15 strong signals were seen in the liver, in the developing bronchial epithelium of the lungs and in the primordial alveoli, in the epithelium of the thyroid gland, in the thymus, in the endochondrial plates of the bone, and in neural cells. The liver from day 15 embryos contained gelatinase activity at 105 kDa consistent with MMP-9. Thus, MMP-9 expression appears to be expressed in specific organs in a precise temporal sequence during development.
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PMID:Developmental expression of MMP-9 (gelatinase B) mRNA in mouse embryos. 856 23

Two patients with histologically proven mycosis fungoides, a malignancy of phenotypically mature T cells, received a topical challenge with mechlorethamine to areas of clinically uninvolved skin to exclude possible hypersensitivity reactions to this chemotherapeutic agent. In both patients, allergic contact dermatitis (ACD) developed at the sites of the application and resolved completely after withdrawal of mechlorethamine. The lesions were biopsied and analyzed for the presence of clonal T-cell receptor (TCR)-gamma gene rearrangements using two polymerase chain reaction (PCR)-based assays involving denaturing gradient gel electrophoresis (PCR/DGGE) and ribonuclease protection analysis (PCR/RPA). The former method has a clonal detection threshold of 10(-3)-10(-2), while the latter has a sensitivity of 10(-5). In both cases, the ACD lesions were polyclonal by PCR/DGGE. In contrast, PCR/RPA detected tumor-specific TCR-gamma gene rearrangements in these same lesions. This indicates that the ACD lesions contained tumor cells at a density within the 10(-5)-10(-2) range. Analysis of peripheral blood mononuclear cells from both patients failed to detect the malignant clone and showed the same result as blood from four normal individuals. The normal skin from one skin patient also lacked detectable TCR-gamma gene rearrangements. These results indicate that mycosis fungoides tumor are present within ACD lesions induced in mycosis fungoides patients and that this phenomenon does not appear to be due to the ubiquitous presence of detectable levels of these tumor cells in the blood or skin. These findings might be explained by nonspecific recruitment of malignant T cells to sites of local inflammation mediated by non-neoplastic antigen-specific T cells. Alternatively, they might be due to the local proliferation of very rare tumor cells in apparently normal skin in response to cytokines generated during the ACD reaction. In either case, the present study offers evidence that the malignant cells in myosis fungoides retain at least some capability of responding in vivo to physiologic stimuli.
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PMID:Detection of low-level tumor cells in allergic contact dermatitis induced by mechlorethamine in patients with mycosis fungoides. 861 5


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