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Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the control by hormones and culture conditions of the expression of pyruvate kinase L, aldolase B, and a liver-specific 5.4-kb mRNA species [Pichard, A. L. et al. (1985) Biochem. J. 226, 637-644] in three rat hepatoma cell lines, MH1C1, Fao and Faza. The expression level of these markers ranges from 2% (for pyruvate kinase L mRNA) to 10-12% (for 5.4-kb mRNA species) of the glucose-induced mRNA values found in rat liver. The mRNAs of the three liver-specific genes strongly decrease after treatment of the hepatoma cells with cyclic 8-bromo-AMP, cyclic dibutyryl-AMP or forkolin, pyruvate kinase L mRNA being the most sensitive to this inhibiting effect. In contrast, the concentration of pyruvate kinase L mRNA nuclear precursors is not modified by the cyclic AMP analogues, indicating that these agents do not act at the transcriptional level but, instead, probably destabilize the transcripts. Glucose or fructose does not modify the expression of these three marker genes in any of the studied cell lines. Insulin is inefficient in modifying concentrations of the mRNAs for pyruvate kinase L and aldolase B, alone or in the presence of carbohydrates. In contrast, it stimulates about fivefold the expression of the 5.4-kb mRNA species in the MH1C1 cell line; this stimulation is carbohydrate-independent. The hepatoma cell lines mimic, therefore, the effect of cyclic AMP on the inhibition in vivo of the expression of genes encoding glycolytic or lipogenic enzymes [Vaulont, S. et al. (1984) Biochem. Biophys. Res. Commun. 125, 135-147]. In contrast, the effect of carbohydrates [Munnich, A. et al. (1984) J. Biol. Chem. 259, 10228-10231] is undetectable. The insulin sensitivity of the liver-specific genes is conserved for the 5.4-kb mRNA species only, especially in the MH1C1 cell line, but not for the other investigated mRNAs, which seems to reflect a fundamental difference in the in vivo effect of insulin on these genes. Finally, S1 nuclease mapping of the start-site of pyruvate kinase L gene transcription shows that the normal site used in vivo is also used in the Fao and Faza lines while, in the MH1C1 line, it coexists with multiple aberrant upstream initiation sites.
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PMID:Regulation of genes for glycolytic enzymes in cultured rat hepatoma cell lines. 369 93

Cell growth using homocysteine as a source of cysteine-sulphur requires two enzymes, cystathionine synthase (CS) and gamma-cystathionase (CT). The second of these enzymes, CT, is apparently present in most cell lines regardless of their tissues of origin, since most cells can grow in vitro in the absence of cystine if they are provided with cystathionine, the intermediate in the pathway. Likewise, homocysteine will support the growth of many human cells. However, of a wide range of rodent cells, only well-differentiated rat hepatoma cells were found to grow using homocysteine in place of cystine. It is shown that cell growth in homocysteine-medium correlates well with the presence in the cells of detectable levels of CS. Furthermore, in cells able to grow in homocysteine-medium, it is possible to demonstrate the homocysteine-dependent trans-sulphuration of serine to cysteine. Growth in homocysteine-medium is not dependent on the release of preformed cysteine from disulphide complexes with serum proteins. In cell hybrids, and in 'dedifferentiated' variants of rat hepatomas, CS, but not CT, is subject to extinction coordinately with well-characterized liver-specific traits. For rodent cells, homocysteine-medium thus acts as a selective medium requiring the expression of a single liver-specific trait, CS. In addition it is shown that, in certain hepatoma variants, CS is regulated co-ordinately with a urea-cycle enzyme (carbamoyl phosphate synthetase I) by glucocorticoids and cyclic-AMP. Cell death through cysteine starvation is briefly considered. The immediate cause of death is apparently an insufficient supply of reduced glutathione. Selenium and vitamin E assist cell growth when the supply of cysteine is limiting.
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PMID:Characterization of cystathionine synthase as a selectable, liver-specific trait in rat hepatomas. 379 84

A study of the enzymes of the glycogen pathway in Novikoff ascites hepatoma shows that glycogen synthetase has the lowest activity and that the tumour contains no high-K(m) soluble glucokinase. However, incubation of tumour cells with metabolizable sugars in vitro, or intraperitoneal administration of glucose into the tumour-bearing rat, results in glycogen accumulation by the tumour cells. Glycogen synthesis in the tumour is supported by aerobically produced ATP but is decreased anaerobically and by uncouplers of oxidative phosphorylation. Absence of P(i) from the incubation medium increases glycogen synthesis and decreases glycolysis. The optimum temperature for glycogen synthesis is 37 degrees . The capacity of the intact tumour cell to degrade deposited glycogen is low, but is accelerated by 2,4-dinitrophenol. Tumour homogenates prepared after osmotic shock do not incorporate [(14)C]glucose into glycogen. The glucose moiety of glucose 1-phosphate and of UDP-glucose is incorporated into glycogen by the homogenates and the incorporation of glucose 1-phosphate is greatly enhanced by AMP. Glucose 6-phosphate is a poor precursor of glycogen in the homogenate system, probably because it inhibits activation of phosphorylase b by AMP.
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PMID:Glycogen metabolism in Novikoff ascites-hepatoma cells. 429 92

A clone of cells in which the regulation of purine metabolism is genetically altered was selected and isolated from chemically mutagenized HTC cells (a line of rat hepatoma cells in continuous culture). The clone, designated MAU V, was selected for increased ability to salvage exogenous purines by isolating it in medium containing methylmercaptopurine ribonucleoside, adenine, and uridine, in which medium wild-type cells cannot divide. We have characterized these cells as having an increased rate of de novo purine biosynthesis, apparently as the result of an altered phosphoribosylpyrophosphate (PRPP) synthetase. The altered enzyme has normal catalytic properties but an altered sensitivity to feedback inhibition by purine and pyrimidine nucleotides. The types of inhibitions (competitive and uncompetitive) exerted by AMP, ADP, and TDP on the wild-type enzyme have been maintained in the altered enzyme, but values for K(i) have been increased by factors of 10, 17.5, and 5, respectively. The specific catalytic activities of AMP: pyrophosphate phosphoribosyltransferase and IMP:pyrophosphate phosphoribosyltransferase are normal. The mutant cell may serve as a model for a specific human disease, one type of dominantly inherited overproduction hyperuricemia.
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PMID:Characterization of a feedback-resistant phosphoribosylpyrophosphate synthetase from cultured, mutagenized hepatoma cells that overproduce purines. 435 85

The growth of rat ascites hepatoma cells (AH 66) in vitro was inhibited and the amount of alpha-fetoprotein (AFP) in the culture medium was increased in the presence of dibutyryl adenosine 3'-5' cyclic monophosphate (DBc-AMP). Electronmicroscopically, AH 66 cells that had been incubated with DBc-AMP showed an increase in polysomes on rough endoplasmic reticulum (RER), and some mitochondria appeared to be completely surrounded by RER. AFP in untreated cells was found to be localized on ribosomes of RER, free ribosomes and occasionally also on microvilli of cell membranes by electronmicroscopic and immunohistochemical analysis. After DBc-AMP treatment, increased staining of AFP was identified on ribosomes of RER and microvilli of cell membranes as well as on nuclear membranes. These results suggest that DBc-AMP accelerates the production and release of AFP in cultured rat ascites hepatoma cells.
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PMID:Effects of dibutyryl adenosine 3'-5' cyclic monophosphate on the ultrastructure of rat ascites hepatoma cells and on the intracellular localization of alpha-fetoprotein. 608 27

'77orn', a derivative of the Morris rat hepatoma 7777, stably expresses high levels of ornithine transcarbamoylase (OTC) and carbamoylphosphate synthetase I (CPS-I), and is able to grow indefinitely in ornithine-medium (medium with ornithine in place of arginine). Variants that have lost this ability are isolated from 77orn by a 'suicide' selective technique dependent on the cellular incorporation of [3H]ornithine. These variants, which have reduced levels of CPS-I, or of both CPS-I and OTC, are shown to have developed multiple hormonal requirements; their enzyme deficiencies can be reversed by use of an appropriately supplemented medium. In particular, CPS-I is inducible by dexamethasone and dibutyryl-cyclic-AMP in combination. Cholera toxin can be used instead of cyclic-AMP, but then butyrate is additionally required if the induction is to be maintained in the long term. The use of these agents in excess can depress OTC. Several other hepatomas, and alos explanted foetal rat liver cells, have similar requirements for CPS-I expression. It is argued that multiple hormonal requirements for CPS-I production are normal in liver cells in vitro, and that hormone-independent hepatomas should be regarded as abnormal. The implications of this for the somatic cell genetic investigation of differentiation are briefly discussed.
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PMID:Arginine synthesis by hepatomas in vitro. II. Isolation and characterization of Morris hepatoma variants unable to convert ornithine to arginine, and modulation of urea-cycle enzymes by dexamethasone and cyclic-AMP. 609 98

The beta-adrenoceptor density and the activities of adenylate cyclase and cyclic AMP phosphodiesterase were examined to compare AH13 cells having lower beta-adrenergic responsiveness with other rat ascites hepatoma cells and normal rat liver cells. Normal rat liver cells used were cultured for 24 hr after the collagenase digestion of liver. The density of binding sites of 3H-dihydroalprenolol in AH13 cell plasma membrane was very similar to the density in AH44 and normal liver cell membrane, but that in AH130 cell plasma membrane was about 10-fold greater than those in the other three cell lines. The activity of cyclic AMP phosphodiesterase was about 2.5- to 7-fold higher in hepatoma cells than in rat liver cells, but this enzyme activity of AH13 cells was not especially high among the hepatoma cells examined. The basal adenylate cyclase activity was lower in AH44 cells, but was higher in AH13 and AH130 cells than in rat liver cells. However, adenylate cyclase of AH13 cells was hardly activated by isoproterenol, while the enzyme of the other cells was activated 3- to 5-fold. On the other hand, adenylate cyclase of each cell line including AH13 was activated 4- to 14-fold by NaF. From these results, it is suggested that AH13 cells can hardly produce cyclic AMP by the beta-adrenergic stimulation because of the disordered interaction of beta-adrenoceptors with adenylate cyclase.
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PMID:Studies on responsiveness of hepatoma cells to catecholamines. I. Lack of beta-adrenergic responsiveness in rat ascites hepatoma AH13 cells. 609 61

Cyclic AMP derivatives increase the rate of synthesis of tyrosine aminotransferase in Reuber H35 hepatoma cells. Various studies lend support to the hypothesis that cyclic AMP increases the synthesis of tyrosine aminotransferase by acting at a posttranscriptional site. The presence of a limited non-translatable pool of tyrosine aminotransferase mRNA prior to the formation of the translatable tyrosine aminotransferase mRNA implicates a possible site of action of cyclic AMP. We compared the capacity of N6,O2'-dibutyryl cyclic AMP to induce tyrosine aminotransferase synthesis when untranslatable tyrosine aminotransferase mRNA sequences are present or absent. The transition of a condition in which non-translatable tyrosine aminotransferase mRNA sequences were present to a condition in which they were absent was established by preinduction of Reuber H35 cells with dexamethasone, followed by addition of actinomycin D. In the time period thereafter, the amount of non-translatable mRNA decreased and 1.5-2 h after addition of actinomycin D, only translatable tyrosine aminotransferase mRNA was present. It can be seen that the induction of tyrosine aminotransferase synthesis by dibutyryl cyclic AMP follows the normal decrease of tyrosine aminotransferase mRNA. We present evidence that dibutyryl cyclic AMP in Reuber H35 hepatoma cells regulates tyrosine aminotransferase synthesis at a posttranscriptional site independent of the pool of non-translatable tyrosine aminotransferase mRNA sequences, but influencing the efficiency of translation of active tyrosine aminotransferase mRNA.
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PMID:Further evidence for translational regulation of tyrosine aminotransferase synthesis by dibutyryl cyclic AMP in Reuber H35 hepatoma cells. 611 49

The following evidence suggests that inhibition of hepatoma cell (HTC) growth by cyclic nucleotides is an adenosine-like effect that is greatly modified by the type and treatment of serum used in the culture medium and is probably not mediated by cyclic AMP-dependent protein kinase: 1) Heating serum reduces its phosphodiesterase content, thereby slowing metabolism of cyclic AMP and reducing the inhibition of HTC cell growth by cyclic AMP; 2) Using medium that contains phosphodiesterase but lacks adenosine deaminase causes adenosine to accumulate from cyclic AMP and increases the toxicity of cyclic AMP; 3) Uridine or cytidine reverses the growth inhibition caused by adenosine, 5'-AMP or cyclic AMP; 4) adenosine, 5'-AMP and N6-(delta 2-isopentenyl) adenosine are more toxic for HTC cells than is cyclic AMP, and N6,O2-dibutyryl cyclic AMP is not toxic; and 5) N6,O2'-dibutyryl cyclic AMP inhibits growth of Reuber H35 cells, but uridine prevents this inhibition of growth. We conclude that most, if not all, of the inhibitory effects of cyclic AMP and N6,O2'-dibutyryl cyclic AMP on HTc and Reuber H35 hepatoma cell growth are due to the generation of toxic metabolites.
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PMID:Inhibition of hepatoma cell growth by analogs of adenosine and cyclic AMP and the influence of enzymes in mammalian sera. 612 49

Five chromatographically distinct DNA-dependent ATPase activities have been identified in high salt-detergent extracts of the Novikoff hepatoma. One of these, ATPase III, has been purified to apparent homogeneity as judged by polyacrylamide gel electrophoresis and has a specific activity of 12 mumol of ATP hydrolyzed min-1 (mg of protein)-1. The enzyme, a dimer of Mr 65000 subunits, has a sedimentation coefficient of 7.0 S in both high salt and low salt, a Stokes radius of 43 A, and a frictional coefficient of 1.31. In the presence of Mg2+ ion and a polynucleotide effector, the enzyme catalyzes hydrolysis of ATP or dATP to a diphosphate with a Km of 206 microM and 110 microM, respectively, for the two substrates. Although single-stranded effectors are preferred, the enzyme has significant activity with double-stranded effectors. The Km for effector is 0.4 microM (nucleotide). The analogues adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), dideoxyadenosine triphosphate (ddATP), and adenosine 5'-(alpha, beta-methylenetriphosphate) (alpha, beta-Me-ATP) are competitive inhibitors of the enzyme while adenosine tetraphosphate (ATP-P), 8-bromoadenosine 5'-triphosphate (8-Br-ATP), 5'-adenylyl imidodiphosphate (AMP-PNP), and adenosine 5'-(beta, gamma-methylenetriphosphate) (beta, gamma-Me-ATP) do not inhibit. The enzyme is insensitive to nalidixic acid, novobiocin, and berenil but is sensitive to N-ethylmaleimide. ATPase III is capable of stimulating DNA polymerase beta on duplex DNA, but this effect is abolished in the presence of ATP gamma S. Polymerase stimulation is further enhanced in the presence of a single-stranded DNA-binding protein. These data suggest that ATPase III may play a role in DNA repair.
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PMID:Deoxyribonucleic acid dependent adenosinetriphosphatases from the Novikoff hepatoma. Characterization of a homogeneous adenosinetriphosphatase that stimulates DNA polymerase beta. 612 27


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