| Increased expression of neprilysin (neutral endopeptidase 24.11) in rat and human hepatocellular carcinomas. | |
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MedLine Citation:
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PMID: 8302012 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Neprilysin (EC 3.4.24.11) (NEP), a membrane metallopeptidase, is identical with common acute lymphoblastic leukemia antigen or cluster differentiation antigen 10. This antigen is present in blast cells in acute lymphoblastic leukemias and is implicated in differentiation of B lymphocytes. NEP cleaves a variety of peptides including bradykinin, substance P, bombesin, enkephalins, and atrial natriuretic peptide. We investigated its expression in several variants of rat hepatomas and a human hepatocellular carcinoma cell line. Normal rat and human livers were used as controls. EXPERIMENTAL DESIGN: The expression of NEP (common acute lymphoblastic leukemia antigen) was determined with: (a) enzyme assays; (b) high performance liquid chromatography analysis of bradykinin metabolism; (c) immunoprecipitation; and (d) mRNA characterization. RESULTS: NEP activity increased by 2 to 3 orders of magnitude in all rat hepatomas and in the human SK-HEP1 cell line, compared with normal tissues. Antiserum against rat NEP precipitated 93% of endopeptidase activity in rat hepatomas, whereas monoclonal antibody to common acute lymphoblastic leukemia antigen immunoprecipitated 99% of that in human hepatocarcinoma cells. Solubilized rat hepatoma membranes cleaved bradykinin to a hepta- and dipeptide; the reaction was inhibited by an NEP inhibitor. Activity of three other membrane peptidases did not increase in rat hepatomas. Northern hybridization revealed the presence of NEP mRNA in rat hepatoma, but not in normal liver. Reverse transcriptase-polymerase chain reaction showed that hepatomas have higher amounts of NEP mRNA than normal liver of the same strain. CONCLUSIONS: Rat hepatomas and a human hepatocarcinoma cell line express high amounts of NEP, in contrast to normal rat and human livers, which have very little. The increase in NEP activity could be due to increased transcription by tumor cells and may signal malignant transformation of liver cells. |
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Authors:
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T Dragović; P A Deddish; F Tan; G Weber; E G Erdös |
Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: Laboratory investigation; a journal of technical methods and pathology Volume: 70 ISSN: 0023-6837 ISO Abbreviation: Lab. Invest. Publication Date: 1994 Jan |
Date Detail:
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Created Date: 1994-03-09 Completed Date: 1994-03-09 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0376617 Medline TA: Lab Invest Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 107-13 Citation Subset: IM |
Affiliation:
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Laboratory of Peptide Research/Department of Pharmacology, University of Illinois College of Medicine, Chicago. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Northern Blotting, Southern Bradykinin / analysis, metabolism Carcinoma, Hepatocellular / chemistry, enzymology*, pathology Cell Membrane / chemistry, enzymology, ultrastructure Chromatography, High Pressure Liquid DNA Probes Gene Expression Regulation, Neoplastic / genetics Humans Liver / chemistry, enzymology Liver Neoplasms / chemistry, enzymology*, pathology Liver Neoplasms, Experimental / chemistry, enzymology*, pathology Neprilysin / analysis*, genetics Polymerase Chain Reaction Precipitin Tests RNA, Neoplasm / analysis, genetics Rats Rats, Inbred ACI Rats, Inbred BUF Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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HL36081/HL/NHLBI NIH HHS; HL36082/HL/NHLBI NIH HHS; HL36473/HL/NHLBI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA Probes; 0/RNA, Neoplasm; 58-82-2/Bradykinin; EC 3.4.24.11/Neprilysin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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