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)

The hepatic acute phase response is accompanied by increased levels of Gal beta 1-4GlcNAc alpha 2,6-sialyltransferase activity in liver and in circulation. Previous studies suggested that cytokines and glucocorticoids mediate the induction of this sialyltransferase activity. In this study the regulation of sialyltransferase expression by dexamethasone in H35 rat hepatoma cells is assessed by Northern hybridization and enzyme activity assays. Exposure of H35 cells to 1 microM dexamethasone for 24 h causes a 3-4-fold enrichment of sialyltransferase mRNA and a corresponding increase in enzymatic activity. The induction of sialyltransferase mRNA begins within 3 h of dexamethasone treatment and reaches a plateau within 24 h. Sialyltransferase mRNA induction is dose dependent; the minimum concentration of dexamethasone necessary for induction is 10(-8) M, and induction was maximal at 10(-6) M. Induction is sensitive to actinomycin D, suggesting that regulation may be exerted by altering the rate of mRNA synthesis. Puromycin and cycloheximide are ineffective in blocking induction, suggesting that de novo protein synthesis is not required for induction. Finally, dexamethasone alone is sufficient for maximum induction of sialyltransferase mRNA. In contrast, maximal induction of alpha 1-acid glycoprotein, a well studied hepatic acute phase reactant, requires both dexamethasone and cytokines, implying that different pathways exist for the induction of participants in the acute phase response.
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PMID:Regulation of beta-galactoside alpha 2,6-sialyltransferase gene expression by dexamethasone. 291 88

The intracellular distribution of galactosyl- and sialyltransferase was investigated in rat hepatocytes of intact liver, primary monolayer cultures of freshly isolated hepatocytes, in a nontumorigenic hepatocyte cell line and in a hepatoma cell line. The two glycosyltransferases were detected by immunofluorescence using affinity-purified rabbit antibodies. Indirect double immunofluorescence showed that both terminal glycosyltransferases were identically codistributed in the same cell. This codistribution was always observed regardless of the cell type investigated, and in both stationary and migrating cells. The immunofluorescence pattern for both galactosyl- and sialyltransferase was found to be different in hepatocytes in vivo compared to hepatocytes grown in vitro. In hepatocytes of intact liver a spot-like cytoplasmic fluorescence was observed, whereas in cultured normal hepatocytes a perinuclear fluorescence from which an extensive tubular network radiated far into the cytoplasm existed. Cultured hepatoma cells also exhibited an extensive cytoplasmic fluorescence, which in contrast to the normal hepatocytes was rather diffuse. We conclude that (a) galactosyl- and sialyltransferase are codistributed in rat hepatocytes, and (b) a reorganization of (trans) Golgi apparatus elements containing both terminal glycosyltransferases occurs under conditions of in vitro growth and malignant transformation.
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PMID:Codistribution of galactosyl- and sialyltransferase: reorganization of trans Golgi apparatus elements in hepatocytes in intact liver and cell culture. 312 31

Sialyltransferases responsible for the formation of sugar chains in glycoproteins were studied in rat hepatoma in comparison with rat liver. Hepatoma induced by feeding Wistar rats with 3'-methyl-4-dimethylaminoazobenzene (MeDAB) was more active than Wistar liver in sialylating asialo-orosomucoid, and this was due to an increased activity of Gal(beta 1----4)GlcNAc (alpha 2----6) sialyltransferase, the major sialyltransferase in these tissues. Gal(beta 1----3,4)GlcNAc (alpha 2----3) sialyltransferase and the sialyltransferase acting on asialo-bovine submaxillary mucin were, however, decreased in the hepatoma. A similar pattern of sialyltransferase alterations was observed in regenerating liver and other tumors such as AH-109A hepatoma and Sato lung cancer, both of which had been inoculated into Donryu rats. In contrast to these sialyltransferases, the activities of the sialyltransferases responsible for the formation of gangliosides were markedly different even between Wistar and Donryu livers. When compared with Wistar liver, MeDAB-induced hepatoma was higher in lactosylceramide- and lower in GM3-sialyltransferase activity, but these two activities were both lower in AH-109A compared with Donryu liver.
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PMID:Comparative study of the levels of sialyltransferases responsible for the formation of sugar chains in glycoproteins and gangliosides in rat liver and hepatomas. 313 1

We have investigated the ganglioside levels, composition and metabolism in two lines of doxorubicin-resistant cells and in the corresponding wild strains, the C6 rat glioblastoma and the HTC rat hepatoma. The only ganglioside present was GM3, and its level was increased 2-fold in C6 resistant cells and decreased nearly 2-fold in HTC resistant cells. A decrease of cytidine 5'-monophospho-N-acetylneuraminic acid:galactosylglucosylceramide sialyltransferase activity was observed in both resistant lines as compared to sensitive ones, and could not, therefore, explain the increase in the GM3 level observed in the C6 resistant line. Alterations of acid neuraminidase activity were also observed; a 5-fold decrease was noticed in the C6 resistant line and could account for the increase in the GM3 level observed in these cells; in contrast, a 2-fold increase of acid neuraminidase activity was noticed in the HTC resistant cells: together, with reduced synthesis, it could explain the decrease in the GM3 level observed in these cells. No alterations of exogenous ganglioside transport was exhibited by the C6 resistant cells.
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PMID:Alteration of ganglioside composition and metabolism in doxorubicin-resistant rat tumoral cells. 319 50

Sialyltransferase was measured in serum of normal and hepatoma Mc-29 bearing chickens. By preparative isoelectric focusing the multiple forms of sialyltransferase from both kind of serums was studied as well. By using influenza virus neuraminidase an attempt was made for partial structural characterization of the sialylation sites in asialofetuin applied as exogenous acceptor for sialyltransferase determination. It was established an elevated serum sialyltransferase activity in tumor bearing chickens with tumor an enzyme form was detected with pI-4.99 identical with an enzyme form described previously in solubilized plasma membrane preparations from hepatoma Mc-29. Monitoring of multiple forms of serum glycosyltransferases may be of value in answering the problem concerning the tissue origin of serum enzymes.
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PMID:Characterization of sialyltransferases from serum of normal and hepatoma Mc-29 bearing chickens. 395 42

In rats bearing a solid form of AH-109A hepatoma, serum asialofetuin sialyltransferase activity was significantly increased. In order to identify the source of the increased serum sialyltransferase, the asialofetuin sialyltransferase activities of normal and host liver, tumor, and normal and host serum were studied by phosphocellulose column chromatography. While normal and host (day 17) livers exhibited two peaks, namely, transferases I and II, which were previously shown to be the sialylated and unsialylated species, respectively, of beta-galactoside alpha 2 leads to 6 sialyltransferase, the tumor exhibited a single peak of the enzyme, which was a sialylated species (as was transferase I) but was eluted at a position clearly distinguishable from that of either transferase I or transferase II. Under these conditions, both normal and host (day 17) sera were found to contain transferase I but not the tumor-type enzyme. The results have been interpreted as indicating that in rats with AH-109A, the tumor is not the source of the increased serum sialyltransferase. In these rats as well as in normal rats, serum sialyltransferase appears to originate mainly from the liver, whose sialyltransferase activity was also increased in rats with AH-109A.
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PMID:Increase in serum sialyltransferase in tumor-bearing rats: the origin and nature of the increased enzyme. 619 46

Multiple forms of microsomal and plasma membrane sialyl and fucosyltransferases from chicken liver and transplantable hepatoma Mc-29 have been separated by means of isoelectric focusing. A net different pattern was distinguished between liver and hepatoma microsomal and plasma-membrane associated transferases. Microsomal sialyltransferase from hepatoma Mc-29 has typical forms with pI = 5.69, 7.43, 8.05 and 8.56, while in plasma membrane, enzymes with pI = 5.00 and 8.70 occur. The presence of 9 forms of fucosyltransferase within the pH range 3.46-9.57 for hepatoma microsomes and within pH 4.52-9.60 for plasma membranes was detected. Forms with pI 5.10, 5.75 and 7.87 could be considered specific for the hepatoma microsomal enzyme, and forms with pI 4.52, 4.85 and 5.20 for the plasma-membrane associated enzyme.
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PMID:Multiple forms of chicken liver and hepatoma Mc-29 microsomal and plasma-membrane sialyl and fucosyltransferases. 653 16

Asialofetuin sialyltransferase from Triton X-100 extracts of rat liver was resolved by phosphocellulose chromatography into two fractions, designated I and II in order of elution. When previously treated with Arthrobacter ureafaciens neuraminidase, fraction I eluted at about the same position as II while no alteration occurred in II. Primary rat hepatomas contained only a single asialofetuin sialyltransferase, identical to fraction I in chromatographic behavior. Transferases I and II were purified to near homogeneity. Transferase II, as well as neuraminidase-treated I, could be sialylated auto-catalytically, indicating that the lack of sialic acid in II is not due to the lack of a sialic-acid-accepting site. Both enzymes formed an (alpha 2 leads to 6)sialylgalactoside linkage with asialo-glycoproteins of the glycosylamine-type and with lactose, and were indistinguishable immunologically. Nevertheless, the transferases exhibited different molecular weights of 37000 (I) and 43000 (II). When heated at 50 degrees C, transferase I lost half its original activity within 20 min while II was scarcely inactivated. Kinetically, transferase I showed three-times higher affinity than II for CMP-N-acetylneuraminic acid and for desialylated plasma membrane. Asialofetuin sialyltransferase was also purified from primary rat hepatoma. The purified enzyme was identical to transferase I in every respect examined. We conclude that hepatomas contain transferase I but lack transferase II.
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PMID:Purification and characterization of beta-galactoside (alpha 2 leads to 6)sialyltransferase from rat liver and hepatomas. 675 21

We isolated the Golgi-rich fraction from rat ascites hepatoma AH-130 cells and rat liver, and compared some properties of glycosyltransferases using various acceptors. The specific activity of sialyltransferase in the hepatoma Golgi fractions was reduced to 19--41% depending upon the acceptor used (asialo-orosomucoid, asialo-fetuin or asialo-mucin), as compared to that of the normal liver Golgi fraction. However, no significant difference between the enzymes from the two sources was observed in pH optimum, requirements for the enzyme activity, and Km values for the donor substrate (CMP-sialic acid) and various acceptors used. The specific activity and other kinetic parameters of hepatoma galactosyltransferase were not significantly different from those of the liver enzyme, when assayed with N-acetylglucosamine, asialo-agalacto-fetuin and asialomucin as acceptors. Glycosyltransferases in the hepatoma and liver Golgi fractions were then assayed with plasma membranes from both sources as exogenous acceptor. Hepatoma sialyltransferase activity was much lower (1/2 to 1/4) than that of the normal liver. Galactosyltransferase activity, however, was found to be slightly higher in the hepatoma Golgi fraction than in the normal liver. Acceptor plasma membranes which were thus glycosylated in vitro by each Golgi enzyme were separated into protein and lipid fractions, and the latter fraction was further analyzed by thin layer chromatography. The results suggest that the hepatoma Golgi had much lower levels of glycoprotein : sialyltransferase and asialo-GM1 : sialyltransferase, but had an increased activity of asialo-GM3 : sialyltransferase. It is also suggested that the hepatoma Golgi had a high activity for the formation of di- and tri-glycosylceramides, for which the liver Golgi showed negligible activity.
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PMID:Characterization of glycosyltransferases in the Golgi complex from rat ascites hepatoma AH-130 cells: a comparison with those from normal liver. 681 67

A human hepatoma cell line (SK-H-MA) released a large amount of sialyltransferase (ST) and galactosyltransferase (GT) into the culture medium, whereas cells derived from normal human liver (Chang) released a large amount of GT but very little ST. The characteristics of hepatoma GT were studied since an abnormal GT isoenzyme has been associated with human gastrointestinal neoplasms. Both hepatoma and Chang medium GT activities had an absolute requirement for MnCl2 (25 mmol/l) and a broad optimal pH between 6.5 and 7.0, and were not affected by 0.1% Triton X-100. These two enzyme preparations were inhibited to the same extent by N-acetylglucosamine and N-acetylgalactosamine, while N-acetylglucosamine was 100 times more potent than N-acetylgalactosamine. Various nucleotides inhibited both enzyme activities equally well. Uracil-containing nucleotides were better inhibitors than thymine-containing nucleotides, and other nucleotides were only slightly inhibitory. The most effective inhibitor was UDP. More of the GT activity in hepatoma medium (65%) as compared to Chang medium (35%) bound to concanavalin A-Sepharose, and was eluted with 2.5% alpha-methylmannoside. These results suggest that the GTs from hepatoma and Chang media are not different in their enzymatic activity but may differ in their carbohydrate contents, which may be another manifestation of the neoplastic nature of the hepatoma cell line.
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PMID:Characterization of galactosyltransferase released from human hepatoma cells. 681 23


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