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)

Angiotensinogen is regulated by both hormones and changes in cardiovascular and electrolyte status. We have used the Reuber H35 (H4IIE) rat hepatoma cell line to study the regulation of angiotensinogen mRNA levels by dexamethasone, aldosterone, L-T3, and 17 beta-estradiol. Using the Acc I (1097 basepairs) fragment of our angiotensinogen cDNA clone, we have studied, by Northern and slot blot analysis, the accumulation of angiotensinogen mRNA in this cell culture system. Angiotensinogen mRNA of approximately 1800 bases was identified in these cells. It was identical in size to angiotensinogen mRNA from rat liver. Cells grown in medium containing serum depleted of thyroid and steroid hormones for up to 72 h showed a progressive decrease in angiotensinogen mRNA. Dexamethasone treatment resulted in a time- and dose-dependent increase in angiotensinogen mRNA. The half-maximal response occurred at 10(-9) M dexamethasone, with a maximal response of approximately 4-fold (serum-free conditions). Aldosterone induced a dose-dependent increase in mRNA. Half-maximal levels were obtained at 5 X 10(-8) M. Competition studies using the glucocorticoid antagonist RU38486 (Roussel-UCLAF) confirmed that dexamethasone was acting through the glucocorticoid receptor and suggested that aldosterone was acting through the same receptor. L-T3 treatment caused a dose and time-dependent increase in angiotensinogen mRNA levels. The half-maximal response occurred at 5 X 10(-8) M, and the maximal response was a 2-fold increase. Combined treatment with dexamethasone and L-T3 triiodothyronine resulted in a synergistic increase in angiotensinogen mRNA levels. 17 beta-Estradiol failed to elicit a change in angiotensinogen mRNA levels consistent with the observation that these cells lack estrogen receptors. Our results indicate that hepatic angiotensinogen mRNA levels are regulated in a complex fashion by several hormones. These cells provide a useful system for studying the hormonal regulation of the angiotensinogen gene.
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PMID:Multiple hormones regulate angiotensinogen messenger ribonucleic acid levels in a rat hepatoma cell line. 359 29

The presence of angiotensinogen messenger RNA (mRNA) was assessed in total RNA extracted from hepatoma, glioma, neuroblastoma, and glioma-neuroblastoma hybrid cell lines. Total RNA from 1 X 10(7) cells was extracted, transferred to a membrane, and hybridized with a 32P-labeled, full-length (1650-base pair) rat angiotensinogen complementary DNA (cDNA). Angiotensinogen RNA sequences could be definitively detected only in hepatoma cells. Steroids were used in an attempt to increase the angiotensinogen mRNA level. Dexamethasone (2 X 10(-6) M) or 17 beta-estradiol (1 X 10(-7) M) was added to the cultures 18 to 24 hours prior to harvest. Dexamethasone treatment of the hepatoma cells resulted in a large increase in angiotensinogen mRNA, whereas estradiol had no effect. Steroids failed to induce detectable levels of angiotensinogen mRNA in total RNA from the other cell lines. That the RNA was intact was ensured by hybridizing duplicate Northern blots to a 32P-labeled actin cDNA. Actin mRNA sequences were detected in all cell lines. Blot hybridization of poly(A)+RNA resulted in the visualization of a weak angiotensinogen mRNA signal for a glioma cell line and a glioma-neuroblastoma hybrid line. However, the ability to detect angiotensinogen mRNA in a cell may depend on the phenotype expressed, which can be governed by culture conditions.
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PMID:Presence of angiotensinogen messenger RNA in various cultured cell lines. 359 87

The generation cycle of an established line of rat hepatoma cells (HTC cells) was studied using synchronized cell techniques. Dexamethasone phosphate (Dex), a synthetic adrenal corticosteriod which induces tyrosine aminotransferase (TAT) in HTC cells randomly distributed in the cell generation cycle, did not affect the durations of the various phases of the cycle. The activities of TAT and several dehydrogenases, and the rates of general protein and RNA synthesis, were studied throughout the cycle.Dex, at 10(-5)M, when added to a synchronized cell population in the latter two thirds of G1 phase or anywhere in the S phase, induces TAT. During the period made up of G2, M, and early G1, Dex does not induce TAT. However, radioisotope incorporation into specifically immunoprecipitated TAT continues during mitosis, when general protein and RNA synthesis are decreased.
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PMID:Synthesis and induction of tyrosine aminotransferase in synchronized hepatoma cells in culture. 438 56

We used a nuclear RNA transcript elongation assay to show that cAMP analogs and dexamethasone cause a selective increase of transcription of the P-enolpyruvate carboxykinase gene in H4IIE hepatoma cells. 8-(4-chlorophenylthio)-cAMP increased transcription within 5 min and the maximal rate, generally 10-15-fold above the basal rate, was attained by 30 min. This increase was of sufficient magnitude to account for the effect on mRNAPEPCK (for example, where PEPCK is phosphoenolpyruvate carboxykinase) accumulation. After the initial increase, and with continued presence of cAMP, transcription of this gene declined to a new steady-state level which was 2-3 times the basal value. The effect of cAMP analogs on P-enolpyruvate carboxykinase gene transcription was obtained in the absence of protein synthesis. This, and the rapidity of the response, indicates that the effect of cAMP is exerted directly on the P-enolpyruvate carboxykinase gene. Dexamethasone results in a specific, 6-fold increase of transcription, sufficient to account for the increase of mRNAPEPCK which follows treatment of H4IIE cells with this glucocorticoid. When 1 nM insulin was added to either untreated H4IIE cells, or cells first treated with a cAMP analog or dexamethasone, there was a marked reduction of cytoplasmic mRNAPEPCK. The inhibitory effect of insulin was readily reversible, as cells regained the basal level of mRNAPEPCK and full responsiveness to cAMP within 1 h after removing insulin. The transcript elongation assay was used to show that insulin inhibits transcription of the gene coding for mRNAPEPCK. The concentration of insulin required for 50% inhibition was 2-5 pM, whereas approximately 200 pM of proinsulin was required to achieve the same inhibition of transcription. This effect was specific, since insulin did not affect the synthesis of total RNA; it was rapid, as 5 nM insulin decreased the rate of P-enolpyruvate carboxykinase gene transcription by 50% within 15 min; and it also does not require ongoing protein synthesis. The magnitude and kinetics of the response suggest that the primary action of insulin in the regulation of P-enolpyruvate carboxykinase synthesis is exerted at the level of mRNAPEPCK transcription. The insulin-mediated inhibition of mRNAPEPCK transcription was noted in untreated cells and in cells first treated with 8-(4-chlorophenylthio)-cAMP, dexamethasone, or both of these agents. Hence, among these compounds, insulin is the dominant regulatory molecule.
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PMID:Multihormonal regulation of phosphoenolpyruvate carboxykinase gene transcription. The dominant role of insulin. 609 65

Dexamethasone, a synthetic glucocorticoid, inhibits the initial rate of transport of the nonmetabolizable amino acid, alpha-aminoisobutyric acid, in rat hepatoma tissue culture (HTC) cells. To determine whether this inhibition is mediated by the same proximal steps as is the steroidal induction of tyrosine aminotransferase, we have examined the hormonal specificity of these two responses for various steroids previously characterized with respect to transaminase induction as agonists, partial agonists, antagonists, or inactive steroids. We conclude that the steroidal inhibition of amino acid transport, at steroid concentrations of 10(-5) M or less is mediated by the same glucocorticoid receptor mechanisms as the induction of tyrosine aminotransferase. First, the concentrations at which the full agonists, dexamethasone and cortisol, produce their half-maximal effects on phenomena are the same. Second, tetrahydrocortisol, which does not interact with the glucocorticoid receptor, neither inhibits transport nor induces transaminase. Third, the competitive interactions between partial agonists or antagonists and the full agonist dexamethasone with respect to both transport inhibition and enzyme induction are virtually identical. At concentrations greater than 10(-5)M, however, both partial agonist and antagonist steroids are capable of fully inhibiting amino acid transport. The effects of these steroids on transport, like those of dexamethasone, are reversible and are blocked by cycloheximide and actinomycin D. Furthermore, these steroids, like dexamethasone, slow the rate of efflux of alpha-aminoisobutyric acid from preloaded cells. Thus, the effects of high concentrations of partial agonist and antagonist steroids on amino acid transport do not appear to reflect a generalized toxic effect on membrane function.
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PMID:Steroid specificity of the glucocorticoid inhibition of amino acid transport in rat hepatoma cells. 611 50

Vitamin B6 metabolism has been investigated in several highly and well-differentiated Morris hepatomas. Comparisons have been made with two poorly differentiated Morris hepatomas, with host livers obtained from tumor-bearing animals, and with fetal, neonatal, and adult rat liver. The pyridoxal phosphate content and the activities of pyridoxine kinase and pyridoxine phosphate oxidase of all Morris hepatomas examined were significantly less than those in adult host or control livers and generally fell in the range determined for fetal and neonatal liver. A similar pattern was not evident for the activity of pyridoxine phosphate phosphatase. Relative to control and host livers, the activity in hepatomas of the pyridoxal phosphate (PLP)-dependent enzyme, ornithine decarboxylase, was generally elevated. Dexamethasone, at a dose which caused an elevation in the activity of PLP-dependent tumor tyrosine aminotransferase, had no effect on PLP metabolism. The data indicate that tumor progression in the Morris hepatoma spectrum in relation to vitamin b6 metabolism falls into an onco-developmental pattern characterized by a diminished amount of tissue PLP and a diminished capability to metabolize precursor vitamer forms to PLP.
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PMID:Vitamin B6 metabolism in liver and liver-derived tumors. 612 59

Gamma-Glutamyltransferase activity was detected in the plasma membrane of the highly differentiated hepatoma cell line Fao, (0.93 mU/mg cell protein). Dexamethasone (1 microM) provoked a 2-3-fold increase in the activity of the enzyme in the presence of fetal calf serum. Maximal induction occurred 48-72 h after addition of the glucocorticoid to the cell culture medium. The hormonal specificity was demonstrated by the relative potencies of several glucocorticoids and sex steroids: hydrocortisone and corticosterone increased gamma-glutamyltransferase activity while tetrahydrocorticosterone and all sex steroids tested were ineffective. The effect of dexamethasone on gamma-glutamyltransferase activity wa specific since the activities of several other plasma membrane enzymes were not modified. The mechanism of the dexamethasone-induced increase in gamma-glutamyltransferase activity was neither by modification of the affinity of the enzyme for its substrates nor by alteration of the subcellular distribution of the enzyme. This increase was prevented by cycloheximide and actinomycin D. The data presented are consistent with a specific glucocorticoid receptor-mediated induction of gamma-glutamyltransferase activity in Fao cells. The kinetic parameters of the induction process by glucocorticoids are very similar to those found in adult rat liver. These results suggest that the Fao cell line is a very convenient system for the study of the molecular mechanisms of glucocorticoid effects on differentiated cells.
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PMID:Glucocorticoid hormones increase the activity of gamma-glutamyltransferase in a highly differentiated hepatoma cell line. 612 16

Dexamethasone, a synthetic glucocorticoid, decreases the plasminogen activator (PA) activity of HTC rat hepatoma cells in tissue culture. Paradoxically, dexamethasone enhances the cyclic nucleotide stimulation of PA activity in these cells 2-4-fold. In this report, we investigated whether this paradoxical glucocorticoids as the induction of tyrosine aminotransferase activity. We compared the concentration-dependences for several classes of steroids, previously classified as full agonists, partial agonists, antagonists or inactive steroids with respect to induction of the transaminase, for both enhancement of cyclic nucleotide stimulation of PA activity and induction of tyrosine aminotransferase activity in parallel cultures. The full agonists dexamethasone and cortisol, the partial agonists deoxycorticosterone and 11 beta-hydroxyprogesterone, the inactive steroid tetrahydrocortisol, and the antagonist 17 alpha-methyltestosterone exhibited similar potencies with respect to both phenomena. Furthermore, when cells were incubated with both dexamethasone and 17 alpha-methyltestosterone, the latter blocked enhancement by dexamethasone in a concentration-dependent fashion. We conclude that glucocorticoid enhancement of cyclic nucleotide stimulation of PA activity is mediated by the same glucocorticoid receptors which mediate direct regulatory effects.
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PMID:Paradoxical effects of glucocorticoids on regulation of plasminogen activator activity. Mediation by glucocorticoid receptors. 614 81

Incubation of rat hepatoma cells with cAMP derivatives stimulates cell-associated plasminogen activator activity 8- to 22-fold and extracellular plasminogen activator activity 30- to 1300-fold. This time- and concentration-dependent increase is enhanced by phosphodiesterase inhibitors. Dexamethasone, a synthetic glucocorticoid, decreases the plasminogen activator activity of these cells, probably through induction of an inhibitor. Paradoxically, dexamethasone, added simultaneously with cAMP derivatives causes a further 4-fold enhancement of the cAMP-mediated stimulation of plasminogen activator activity. Dexamethasone also alters the time course of cAMP-mediated enhancement of plasminogen activator activity: increased protease activity is detected at 4 hr in cells incubated with 8-bromoadenosine-3':5'-cyclic monophosphoric acid and 1-methyl-3-isobutylxanthine but not until 12 hr in cells incubated with dexamethasone as well. Glucocorticoids thus exert two separate and opposite effects on plasminogen activator activity: induction of an inhibitor and amplification of cyclic nucleotide action. Although permissive and synergistic effects of dexamethasone on cyclic nucleotide action have been reported previously, glucocorticoid regulation of plasminogen activator activity is unique in that the amplification of cyclic nucleotide effects by dexamethasone opposes its regulatory action toward a specific enzyme.
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PMID:Paradoxical effects of glucocorticoids on regulation of plasminogen activator activity of rat hepatoma cells. 617 95

The activity of tyrosine aminotransferase (TAT) decreased biphasically in livers of rats fed 3'-methyl-4-dimethylaminoazobenzene (3'-MDAB). TAT activity decreased to an extremely low level at later stages of hepatocarcinogenesis. The activity of TAT is negatively correlated with alpha-fetoprotein (AFP) levels. The level of TAT enzyme activity in precancerous liver and hepatoma is a reflection of the amount of TAT mRNA. Dexamethasone increased the TAT enzyme activity and TAT mRNA concentration in rat livers during chemical carcinogenesis.
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PMID:Changes in hepatic levels of tyrosine aminotransferase messenger RNA during chemical hepatocarcinogenesis. 620 Feb 5


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