Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

alpha-Fetoproteins (AFPs) were purified from 2 hepatoma cell lines (Hep G2 and HuH-7) and a hepatoblastoma cell line (HuH-6), and the structures of pyridylaminated (PA) derivatives of their sugar chains were analyzed by HPLC. Simultaneously, the activities of alpha 1-6 fucosyltransferase (alpha 1-6FT) and N-acetylglucosaminyltransferase III (GnT-III), IV (GnT-IV) and V (GnT-V) were assayed in these cell lines. For all 3 cell lines the major sugar chain detected was a fucosylated biantennary structure. Hep G2 cells contained a high level of GnT-V, which catalyzes the formation of a tri'-antennary structure, and in fact a substantial percentage of the AFP sugar chains in these cells had the tri'-antennary structure. alpha 1-6FT was also high, and fucosylated tri' structures were detected, which suggests that high activities of transferases affect the AFP sugar chains. In HuH-6 cells, GnT-III, which catalyzes the formation of bisecting GlcNAc, was elevated. Correspondingly, a fucosylated, bisected biantennary structure was found as a major sugar chain. In the HuH-7 cell line, the contents of bisecting GlcNAc and tri' structure were low and neither GnT-III nor GnT-V was elevated. These data indicate that the sugar structures of AFP in these cell lines correlate well with the activities of alpha 1-6 FT, GnT-III and GnT-V.
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PMID:Enzymatic basis of sugar structures of alpha-fetoprotein in hepatoma and hepatoblastoma cell lines: correlation with activities of alpha 1-6 fucosyltransferase and N-acetylglucosaminyltransferases III and V. 137 6

N-Acetylglucosaminyltransferase III, IV and V activities were assayed in various rat tissues and hepatomas using the same fluorescence-labeled sugar chain, GlcNAc beta 1-2Man alpha 1-3-(GlcNAc beta 1-2Man alpha 1-6)Man beta 1-4GlcNAc beta 1-4GlcNAc-2-aminopyridine as a substrate. The N-acetylglucosaminyltransferase III activity toward the substrate is the highest in most rat tissues including primary rat hepatoma. A relatively higher activity for GnT-V is found in small intestine, serum and hepatoma as compared to that of GnT-IV. Some kinetic properties of these enzymes in crude extracts were also determined.
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PMID:Determination of N-acetylglucosaminyltransferases III, IV and V in normal and hepatoma tissues of rats. 214 37

An N-acetylglucosaminyltransferase III which catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage (bisecting N-acetylglucosamine) to the beta-linked mannose of the trimannosyl core structure of N-linked oligosaccharides of glycoproteins was measured in human serum, and liver and hepatoma tissues. The enzyme activity in serum was significantly elevated in patients with hepatomas and liver cirrhosis, and the activity markedly decreased on the transcatheter arterial embolization treatment. High activities were also found in the hepatoma and cirrhotic liver tissues, indicating that the serum activity reflected the activity in the tissues. The assaying of the enzyme activity in serum appears to be useful for the detection and monitoring of primary hepatomas.
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PMID:N-acetylglucosaminyltransferase III in human serum, and liver and hepatoma tissues: increased activity in liver cirrhosis and hepatoma patients. 248 96

The activity of N-acetylglucosaminyltransferase III, which adds a "bisecting" GlcNAc in beta 1,4 linkage to the beta-linked Man of the core of Asn-linked oligosaccharides (Narasimhan, S. (1982) J. Biol. Chem. 257, 10235-10242), was determined in hepatic nodules of rats initiated by administration of a single dose of carcinogen 1,2-dimethylhydrazine.2HCl (100 mg/kg, intraperitoneal) 18 h after partial hepatectomy and promoted by feeding a diet supplemented with 1% orotic acid for 32-40 weeks. N-Acetylglucosaminyltransferase III was assayed using glycopeptide GlcNAc beta 1,2Man alpha 1,6(GlcNAc beta 1,2Man alpha 1,3)Man beta 1, 4GlcNAc beta 1,4GlcNAc-Asn as substrate and, as enzyme sources, microsomal membranes of the hepatic nodules, surrounding liver, regenerating liver, and age- and sex-matched control liver. The nodules had significant N-acetylglucosaminyltransferase III activity (0.78-2.18 nmol GlcNAc transferred/h/mg of protein), while the surrounding liver, the regenerating liver (24 h after partial hepatectomy), and the control liver had negligible activity (0.02-0.03 nmol/h/mg of protein). Product isolated from a large scale N-acetylglucosaminyltransferase III incubation with hepatic nodules as enzyme source showed the presence of the bisecting GlcNAc residue by 500 MHz proton NMR spectroscopy. Concomitant with the appearance of N-acetylglucosaminyltransferase III activity in the preneoplastic nodules, the activities of N-acetylglucosaminyltransferase I and II were decreased in these membranes when compared to those from surrounding liver, regenerating liver, and control liver. These results suggest that N-acetylglucosaminyltransferase III is induced at the preneoplastic stage in liver carcinogenesis promoted by orotic acid and are consistent with the reported presence of bisecting GlcNAc residues in the Asn-linked oligosaccharides of rat and human hepatoma gamma-glutamyl transpeptidase and their absence in enzyme from normal liver of rats and humans (Kobata, A., and Yamashita, K. (1984) Pure Appl. Chem. 56, 821-832).
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PMID:Expression of N-acetylglucosaminyltransferase III in hepatic nodules during rat liver carcinogenesis promoted by orotic acid. 296 50

Ascites hepatoma AH-66 and 3'-Me-DAB-induced hepatoma of rats contain highly active N-acetylglucosaminyltransferase III (GnT-III) which catalyzes the addition of N-acetylglucosamine through a beta 1-4 linkage (bisecting N-acetylglucosamine) to the beta-linked mannose of the trimannosyl core of asparagine-linked sugar chains, whereas normal rat liver contains very little. The high activity was also detected in fetal rat liver, newborn rat liver, hyperplastic nodules and various transplantable hepatomas.
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PMID:High expression of an N-acetylglucosaminyltransferase III in 3'-methyl DAB-induced hepatoma and ascites hepatoma. 298 Oct 47

The LEC (Long-Evans with a cinnamon-like color) rat is a mutant of the Long-Evans strain which develops hereditary hepatitis and hepatoma with age. Activities and mRNA levels of N-acetylglucosaminyltransferase III and V (GnT-III and GnT-V, respectively) were determined during hepatocarcinogenesis in this rat using a LEA (Long-Evans with an agouti color) rat as a control. GnT-III activity in LEC rat liver increased after 30 weeks of age, at the stage of chronic hepatitis, to about 2.5-11.5 times the level in LEC rats aged 1-9 weeks. GnT-V activity in the LEC rat liver increased after 20 weeks of age, at the stage of acute hepatitis, to about 1.5-2.5 times the level in LEC rats of 1-9 weeks of age and then remained elevated. Both enzymes showed more dramatic increases in males than in females. The mRNA levels of the enzymes increased in proportion with the enzyme activities. Furthermore, GnT-III and GnT-V mRNAs were highly expressed in both cancer lesion and adjacent tissues. In one case of hepatoma with lymph node metastasis, GnT-III and GnT-V mRNA expression was much higher in the metastatic lesion than in the original cancer. GnT-III and GnT-V levels in the original cancer lesions were similar to those in the cancer lesions of the other LEC rats. These results indicated that expression of GnT-III and GnT-V was induced by chronic liver damage and hepatocarcinogenic changes in the LEC rats.
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PMID:N-acetylglucosaminyltransferase III and V messenger RNA levels in LEC rats during hepatocarcinogenesis. 824 May 32

The antisense cDNA of N-acetylglucosaminyltransferase V (GnT-V, EC 2. 4.1.155) was constructed as pcDNA3/GnT-V-AS plasmid and transfected into 7721 cells, a human hepatocarcinoma cell line. The transfection was confirmed with Northern blot. By using HPLC and HRP-lectin staining, it was found that the cells transfected with pcDNA3/GnT-V-AS (GnT-V-AS/7721) expressed less GnT-V activity and beta-1,6-GlcNAc branching in the cell glycoproteins compared with the cells mock-transfected with the vector pcDNA3 (pcDNA3/7721). The growth rate of GnT-V-AS/7721 was decreased in serum-containing medium, while the cell death was accelerated in serum-free medium. The GnT-V-AS/7721 cells were more susceptible to the apoptosis induced by ATRA than the mock-transfected cells. This was evidenced by the obvious appearance of a hypoploid sub-G(1) fraction in the DNA histogram using FCM analysis, the more condensed new moon-type nuclei under morphological observation, and the more intensive TUNEL reaction for assaying the fragmented DNA. At the same time as GnT-V down-regulation by GnT-V-AS, an increase of another N-aceylglusaminyltransferase, GnT-III (EC 2.4.1.144), was observed, and the biological significance of this finding was discussed.
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PMID:Increased susceptibility to apoptosis of human hepatocarcinoma cells transfected with antisense N-acetylglucosaminyltransferase V cDNA. 1052 94

In this paper, uridine diphosphate (UDP)-N-acetylglucosamine/beta-D-mannoside beta-1,4 N-acetylglucosaminyltransferase III (GlcNAc-transferase-III C 2.4.1.144) activity was determined in human hepatoma cell lines of Hep3B and HepG2, and also compared with those of normal liver tissues and primary hepatocytes. GlcNAc-transferase-III enzymes of Hep3B and HepG2 were mainly detected in the membrane fraction. When GlcN,GlcN-biant-PA and UDP-GlcNAc were used as substrates, the Km values (4.7 mM for UDP-GlcNAc and 1.1 mM for GlcN, GlcN-biant-PA) of Hep3B GlcNAc-transferase-III were distinguishable from those of HepG2 GlcNAc-transferase-III (6.8 mM for UDP-GlcNAc and 3.4 mM for GlcN,GlcN-biant-PA). Furthermore, Hep3B enzyme in membrane fraction showed about 1.5-fold higher specific activity (1423 pmol/hr/mg) than that of HepG2 (1066 pmol/hr/mg). Normal liver cells and primary adult hepatocytes are characterized by a very low level of GlcNAc-transferase-III activity, whereas human hepatoma cells exhibited high activities. These data were supported by reverse transcription-polymerase chain reaction results, showing that expression of the GlcNAc-transferase-III mRNA increased in proportion to the enzymatic activities. Although the mechanism underlying the induction of this enzyme is unknown, lectin blot analysis showed that oligosaccharides in many glycoproteins were observed in hepatoma cells. By treating hepatocarcinoma cultures that express GlcNAc-transferase-III with inhibitors (tunicamycin, deoxymannojirimycin, and swainsonine) of different steps of the glycosylation, we provide evidence that expression of GlcNAc-transferase-III mRNA is dependent on glycosylation of cellular proteins.
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PMID:Expression of bisecting N-acetylglucosaminyltransferase-III in human hepatocarcinoma tissues, fetal liver tissues, and hepatoma cell lines of Hep3B and HepG2. 1176 33

N-acetylglucosaminyltransferase III (GlcNAc-TIII), a product of the human MGAT3 gene, was discovered as a glycosyltransferase activity in hen oviduct. GlcNAc-TIII transfers GlcNAc in beta4-linkage to the core Man of complex or hybrid N-glycans, and thereby alters not only the composition, but also the conformation of the N-glycan. The dramatic consequences of the addition of this bisecting GlcNAc residue are reflected in the altered binding of lectins that recognize Gal residues on N-glycans. Changes in GlcNAc-TIII expression correlate with hepatoma and leukemia in rodents and humans, and the bisecting GlcNAc on Asn 297 of human IgG antibodies enhances their effector functions. Overexpression of a cDNA encoding GlcNAc-TIII alters growth control and cell-cell interactions in cultured cells, and in transgenic mice. While mice lacking GlcNAc-TIII are viable and fertile, they exhibit retarded progression of diethylnitrosamine (DEN)-induced liver tumors. Further biological functions of GlcNAc-TIII are expected to be uncovered as mice with a null mutation in the Mgat3 gene are challenged.
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PMID:Biological consequences of overexpressing or eliminating N-acetylglucosaminyltransferase-TIII in the mouse. 1241 19

A glycomic approach to the identification of target molecules in glycosyltransferase gene targeting mice is a promising strategy to understand the biological significance of glycosyltransferase genes in vivo. In order to understand the biological effects of N-acetylglucosaminyltransferase III (GnT-III) on tumor formation in the liver, diethylnitrosamine (DEN) induced tumor formation in the GnT-III transgenic mice was examined. Our findings show that the incidence of hepatic tumor could be dramatically suppressed. A glycomic approach using two-dimensional gel electrophoresis followed by lectin blot analysis and sequence analysis revealed that haptoglobin, a radical scavenger molecule in serum was heavily glycosylated in hepatic tumor-bearing GnT-III transgenic mice that had been treated with DEN. Immunoprecipitation followed by E4-PHA lectin blot analysis also confirmed that the bisecting GlcNAc, a product of GnT-III was added to haptoglobin molecules. Since the use of DEN is known to lead to the production of lipid peroxidation products which facilitate this reaction and haptoglobin is an acute phase reactant, acting as a radical scavenger against hemoglobin or iron stimulated lipid peroxidation, a relationship between the glycosylation of haptoglobin and the suppression of hepatoma development can not be ruled out. This paper is the first report that shows a relationship between the sugar chains of glycoproteins with radical scavenger activity and hepatocarcinogenesis.
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PMID:A glycomic approach to hepatic tumors in N-acetylglucosaminyltransferase III (GnT-III) transgenic mice induced by diethylnitrosamine (DEN): identification of haptoglobin as a target molecule of GnT-III. 1242 Jul 40


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