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)

1. The possibility of an effect of zinc on the rate of tumour cell division, mediated through a regulation of cellular cAMP concentration, was investigated in the present study in rats. 2. Dietary Zn deficiency (less than 1.5 mg Zn/kg) but not Zn excess (500 mg Zn/kg) resulted in an increased cAMP concentration in transplanted hepatoma cells. Neither treatment had any effect on the cAMP concentration in regenerating liver or normal resting liver. Both the deficient and excess Zn diets resulted in a small reduction in tumour growth (not statistically significant). 3. The results seem to indicate that the relation investigated in the present study does not apply in the cell line used.
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PMID:A possible relation between dietary zinc and cAMP in the regulation of tumour cell proliferation in the rat. 284 Jan 15

Two H4IIE hepatoma cell genes, phosphoenolpyruvate carboxykinase (PEPCK) and gene 33 (g33), are reciprocally regulated by insulin. Quantitation of mRNAPEPCK and mRNAg33 in total RNA isolated from cells treated with insulin showed a 7-fold increase in mRNAg33 amount and a 3-fold decrease of mRNAPEPCK. The cAMP analog 8-(4-chlorophenylthio)-cAMP induced mRNAPEPCK but had no effect on mRNAg33. The responses to various insulins and related molecules showed that the insulin receptor mediates the effects of physiologic concentrations of insulin on each of these genes. This inverse pattern of regulation by insulin was further characterized by determining the transcription rates of both genes in nuclei isolated at various times after the addition of insulin and 8-(4-chlorophenylthio)-cAMP to H4IIE cells. Insulin increased the rate of synthesis of mRNAg33 from 35 to 354 ppm and decreased the synthesis of mRNAPEPCK from 1175 to 109 ppm. These effects of insulin occurred rapidly and reached their maxima by 60 min. In both cases, greater effects were observed as insulin concentrations were increased from 10(-12) to 10(-8) M. Although the effects of insulin were concentration-dependent for both genes, the PEPCK gene was significantly more sensitive to low concentrations of insulin than was gene 33. The reciprocal effects of insulin on the synthesis of mRNAPEPCK and mRNAg33 in H4IIE cells provide a means of investigating how a hormone can exert opposing effects on two genes in the same cell.
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PMID:Reciprocal regulation of gene transcription by insulin. Inhibition of the phosphoenolpyruvate carboxykinase gene and stimulation of gene 33 in a single cell type. 284 5

A 24h pretreatment of the human hepatoma cell line HepG2 with dibutyryl cyclic AMP in the presence of theophylline induced a dose dependent decrease in low density lipoprotein binding, uptake and degradation. This effect is most likely due to a reduction of the LDL receptor number. Sterol synthesis from sodium acetate is markedly inhibited, either in the presence or absence of LDL, whereas synthesis from mevalonic acid is unchanged. Cyclic AMP also induced a decrease in hydroxy methyl glutaryl coenzyme A reductase activity. These effects of cyclic AMP might be involved in some hormonal regulation of the LDL pathway and cholesterol metabolism in the liver.
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PMID:Cyclic AMP decreases LDL catabolism and cholesterol synthesis in the human hepatoma cell line HepG2. 284 80

Hepatoma cells were infected with replication-incompetent murine retroviruses containing the selectable gene for amino-3'-glycosyl phosphotransferase (neo) and/or the nonselectable gene for bovine growth hormone (bGH). Expression of these genes was controlled by the promoter regulatory region of the gene for the cytosolic form of phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) from the rat, which contains hormone and tissue-specific regulatory elements. Expression of the transduced PEPCK-neo gene was stimulated by Bt2cAMP and glucocorticoids and inhibited by insulin. The amount of RNA which initiated within the retroviral 5' long terminal repeat (5' LTR) was inhibited when internal promoters were present in the retroviral vector. When no internal promoter was present, expression from the 5' LTR was higher and stimulated by glucocorticoids, due to the presence of a glucocorticoid regulatory element in the 5' LTR. Infection of cells with retroviruses altered the basal expression and hormonal regulation of the endogenous PEPCK gene, but had no effect on the expression of the tyrosine aminotransferase gene, which is regulated in a similar manner by cAMP and glucocorticoids. A segment of the PEPCK promoter acted as a hormonally regulated enhancer, bringing the SV40 early promoter under the control of Bt2cAMP. A second, nonselectable gene (PEPCK-bGH), contained in the retroviral vector together with PEPCK-neo, was expressed and regulated appropriately when introduced into hepatoma cells. The proviruses were initially integrated randomly into the host cell genome, but after prolonged selection for expression of the transduced PEPCK-neo gene, cells were selected which contain a predominant site(s) of integration. Among populations of cells, however, the predominant site(s) of proviral integration was different. The selection of cells with a specific site of integration from a population was accelerated by the presence of PEPCK promoter sequences in the provirus. Despite the need to better characterize their effects on the host cell, retroviruses appear to be versatile tools for the specific introduction of regulated genes into cells.
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PMID:Hormonal regulation of chimeric genes containing the phosphoenolpyruvate carboxykinase promoter regulatory region in hepatoma cells infected by murine retroviruses. 284 79

cAMP and phorbol esters mediate cellular metabolism by the activation of distinct signal transduction pathways consisting of a cascade of sequential protein phosphorylations. An important consequence of the activation of these pathways is the stimulation of gene transcription by way of interactions of specific proteins with DNA control elements. The 8-base-pair (bp) DNA consensus sequence TGACGTCA [cAMP response element (cAMP-RE)] has been shown to confer cAMP responsivity on transcription from various promoters, and the closely related 7-bp consensus sequence TGA-(C or G)TCA [phorbol 12-myristate 13-acetate response element (PMA-RE)] lends transcriptional responsiveness to phorbol esters. In the JEG-3 placental cell line we find that several variants of the cAMP-REs fused to a gonadotropin alpha promoter chloramphenicol acetyltransferase reporter gene mediate responsiveness to cAMP but not to phorbol esters. The PMA-RE is responsive to phorbol esters but also imparts submaximal sensitivity to cAMP in the JEG-3 cells and in the Hep G2 hepatoma cell line. The transcriptional activities of cAMP-RE and PMA-RE are markedly influenced by the composition of the neighboring bases, but different sequences are permissive for the activity of the cAMP-RE versus the PMA-RE. The two signaling agents together display a supraadditive effect on reporter genes containing active PMA-REs but not cAMP-REs. Gel-mobility-shift and UV cross-linking analyses show that distinct proteins bind to the two control elements. One protein of 38 kDa binds to the cAMP-RE and several proteins of 48-84 kDa bind to the PMA-RE.
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PMID:Cyclic AMP and phorbol ester-stimulated transcription mediated by similar DNA elements that bind distinct proteins. 284 47

Protein kinase activity toward the 40 S ribosomal protein S6 is activated 6-fold in regenerating rat liver following 70% hepatectomy. The kinase is maximally activated within 2 h after surgery, remains active up to 36 h after surgery, and declines rapidly thereafter. The post-hepatectomy S6 kinase activity exhibits structural and functional similarity to an insulin-stimulated S6 kinase in H4 hepatoma cells. Both S6 kinase activities are cAMP- and Ca2+-independent, and have a requirement for [ethylenebis(oxyethylenenitrilo)]tetraacetic acid. The regenerating liver and the insulin-stimulated H4 hepatoma S6 kinase elute at similar positions when sequentially fractionated by anion-exchange and cation-exchange chromatography. Both enzymes migrate at Mr 70,000 on fast protein liquid chromatography Superose 12 gel filtration. In H4 hepatoma cells, activation of S6 kinase activity is reversed by removal of insulin, and the cells can then be restimulated. Freshly isolated hepatocytes from normal animals show low levels of S6 kinase activity which can be stimulated by epidermal growth factor and insulin. Hepatocytes prepared from regenerating liver remnant have constitutively high levels of S6 kinase activity, which is unresponsive to insulin plus epidermal growth factor and which remains elevated at least 2 h in the absence of exogenously added growth factors. These findings demonstrate S6 protein kinase activation in vivo, in the setting of regulated cell growth; as in cultured cells, activation of S6 kinase probably represents an early step in the pleiotypic response elicited by activation of growth factor receptors.
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PMID:An S6 kinase activated during liver regeneration is related to the insulin-stimulated S6 kinase in H4 hepatoma cells. 284 28

A new polysaccharide compound (ACPS-R) has recently been isolated from the root of Actinidia Chinensis Planch. When given intraperitoneally to the transplantable tumor bearing mice at dose of 75-125 mg/kg, the tumor inhibition rate was more than 88.8% in Ehrilich ascitic cancer (EAC) or ascitic form of hepatoma (HepA) and more than 49.6% in solid hepatoma (HepS). The treatment effect of ACPS-R on EAC at dose of 15 mg/kg and 22.5 mg/kg, respectively. ACPS-R could also prolong the life of EAC-or P388-bearing mice, and increase the percentage of EAC-free mice. In addition, when ACPS-R was used in combination with 5-Fu, the antitumor effect was enhanced as compared with 5-Fu alone. A marked increase in cAMP levels and cAMP/cGMP ratio of spleen of EAC-bearing mice were observed after treatment of ACPS-R. The increase of both parameters nearly reached the normal levels of healthy mice. The increases of cAMP, cAMP/cGMP and tumor remission had statistical significance. It showed an intermediate inhibitory effect of ACPS-R on DNA synthesis by incorporating 3H-TdR into EAC cells. The results indicated that ACPS-R acts as a new antitumor polysaccharide, and the treatment effect of Actinidia root in folk medicine is probably related to ACPS-R.
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PMID:[Antitumor effect of actinidia chinensis polysaccharide on murine tumor]. 285 56

The purpose of these studies was to determine whether the catalytic subunit of cAMP-dependent protein kinase is involved in the regulation of P-enolpyruvate carboxykinase (PEPCK) gene transcription. Cyclic AMP analog pairs that preferentially stimulate either type I or type II protein kinase in a synergistic manner were used to compare regulation of mRNAPEPCK synthesis in H4IIE rat hepatoma cells with protein kinase activation in vitro. Type II protein kinase is predominant in H4IIE cells and analog pairs directed toward this isozyme resulted in a synergistic increase of mRNAPEPCK that was due to a corresponding enhancement of PEPCK gene transcription. When compared to a single analog the addition of a type II-directed analog pair reduced the total analog concentration required for maximal induction of transcription by about 30-fold. H4IIE cells have a small amount of type I kinase; pairs specific for this form of the enzyme were also effective, but to a lesser extent than those for the type II kinase. (Rp)-cAMPS, a cyclic nucleotide-dependent protein kinase antagonist, inhibited the agonist-induced increase of mRNAPEPCK in a concentration-dependent manner. The results indicate that the activation of PEPCK gene transcription by cAMP in H4IIE cells is mediated by cAMP-dependent protein kinase. Although the type II isozyme is primarily responsible, type I is also effective. These isozymes have identical catalytic subunits, hence this component presumably mediates the cAMP effect.
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PMID:Regulation of phosphoenolpyruvate carboxykinase gene transcription in H4IIE hepatoma cells: evidence for a primary role of the catalytic subunit of 3',5'-cyclic adenosine monophosphate-dependent protein kinase. 285 13

The hormone-responsive enzymes tyrosine aminotransferase and glycerol-3-phosphate dehydrogenase were studied with respect to current models of the mechanism of glucocorticoid/cAMP interaction during the induction of enzyme activity in responsive cell hybrids between rat C6 glioma cells and rat FU5AH hepatoma cells. The results of experiments involving protein and mRNA synthesis inhibitors, sequential addition of inducers, and the assay of cyclic-AMP-dependent protein kinase could not be adequately explained by any one model of inducer interaction. Comparison of the hybrid clones revealed the presence of factors that may modify induction but that are not essential for synergistic induction.
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PMID:The synergistic interaction of hydrocortisone and dibutyryl cyclic AMP during enzyme induction in hybrids between rat C6 glioma cells and FU5AH hepatoma cells. 286 87

The effect of insulin on the abundance of mRNAs coding for tyrosine aminotransferase (TAT; EC 2.6.1.5), tryptophan oxygenase (TO; EC 1.13.1.12), and P-enolpyruvate carboxykinase(GTP) (PEPCK; EC 4.1.1.32) was examined in primary cultures of adult rat hepatocytes and in FTO-2B rat hepatoma cells by Northern blot analysis using RNA probes made from SP6-cDNAs. Insulin (10(-11)-10(-7) M), which has been reported to induce TAT and decrease the activity of TO, did not change the levels of TAT mRNA and TO mRNA in hepatocytes regardless of the presence of other inducers. In the same cells, dexamethasone increased TAT mRNA up to 19-fold and TO mRNA up to 15-fold, and 8pClPhS-cAMP (CPT-cAMP) raised the level of TAT mRNA up to 36-fold. The abundance of TO mRNA was not altered by CPT-cAMP. In contrast to TAT mRNA and TO mRNA, the level of PEPCK mRNA was dramatically decreased by insulin in the same hepatocytes. The sensitivity to this inhibitory effect of insulin was enhanced by dexamethasone and reduced by CPT-cAMP. FTO-2B hepatoma cells, which do not express detectable levels of TO mRNA, showed responses similar to those of hepatocytes, except that insulin caused a moderate reduction in TAT mRNA, but only in the presence of CPT-cAMP. The PEPCK mRNA in FTO-2B cells was suppressed by insulin in a manner closely resembling the effects in hepatocytes in the present study and in H4IIE hepatoma cells previously reported.
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PMID:Regulation of gene expression in rat hepatocytes and hepatoma cells by insulin: quantitation of messenger ribonucleic acid's coding for tyrosine aminotransferase, tryptophan oxygenase, and phosphoenolpyruvate carboxykinase. 287 68


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