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)

Whereas glucocorticoids induce TAT, TRP, GPT in liver and only TAT in HTC cells, no hormonal effect on the synthesis of these enzymes was found in Zajdela hepatoma cells grown in vivo as an ascitic tumor, or in vitro as layer cultures. Although these cells remain uninducible, the hormone penetrates normally, but a strong decrease of the specific binding of cytosol and nuclear proteins with the hormone was observed. The impairment at the level of the hormone receptors could account for the non-inducibility of enzyme synthesis in ZHC cells.
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PMID:Impairment of enzyme induction by glucocorticoids in Zajdela hepatoma cells. 1 35

The effect(s) of lack of dietary pyridoxine (PX) on the growth of Morris hepatoma no. 7288Ctc was studied. Buffalo strain female rats were fed a diet lacking PX. Pair-fed controls were fed the same diet with PX added. Animals were inoculated with no. 7288Ctc hepatoma cells at 21 days and were sacrificed 16 days later. Host livers and tumors were removed, weights recorded and the activity of tyrosine aminotransferase (TAT; L-tyrosine: 2-oxoglutarate aminotransferase, EC 2.6.1.5) was determined in both host liver and hepatoma. The average weight of 30 hepatomas grown in pair-fed control rats was 11.61 +/- 1.5 g while the average weight of the same number of hepatomas grown in animals fed the PX free diet was 4.73 +/- 0.7 g (P less than 0.001). Further TAT specific activity levels were 39% and 32% higher in host livers and tumors from deficient animals, respectively. The results show that availability of dietary pyridoxine stimulates the growth of this hepatoma and, in addition, exercises a type of control over the expression of TAT activity.
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PMID:Effect of pyridoxine on the growth of Morris hepatoma No. 7288Ctc and enzyme activity. 1 84

Relying heavily on studies of TAT regulation in cultured rat hepatoma cell lines, we have attempted in this brief review to discuss possible mechanisms for posttranscriptional regulation of glucocorticoid-sensitive enzymes and to chronicle the evidence for and against posttranscriptional mechanisms for specific enzyme induction by glucocorticoids. Initially, mechanisms were considered that would reconcile results showing sensitivity of both induction and deinduction of TAT to inhibitors of RNA synthesis with studies demonstrating first that glucocorticoids regulate the rates of specific enzyme synthesis and, then, that glucocorticoids regulate levels of enzyme-specific mRNA. Such reconciliation proved unnecessary when it was demonstrated that inhibitors of RNA synthesis such as actinomycin D were not specific for RNA synthesis, but also had effects on mRNA turnover and protein metabolism. The bulk of evidence to date establishes that glucocorticoids promote the production of enzyme-specific mRNA for the proteins whose synthesis is regulated by thses steroids. Nevertheless, there is still very little direct evidence that steroids can modulate rates of specific gene transcription. The glucocorticoid stimulation of mouse mammary tumor virus RNA production in cultured cell lines is the only example to date where such a mechanism is supported by RNA-DNA hybridization studies. Posttranscriptional actions of steroids on the turnover, processing, or extranuclear transport of specific mRNA precursors remain potential steps at which glucocorticoids might function. The rapid turnover of some glucocorticoid-regulated enzymes and their mRNAs not only ensures a rapid response to steroid addition or withdrawal, but also subjects these proteins to relatively large fluctuations upon alterations in overall protein or mRNA metabolism. Thus many of the inductions and repressions of hepatic TAT and TO by mediators other than the glucocorticoids may be attributable entirely to nonspecific mechanisms.
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PMID:Posttranscriptional regulation of glucocorticoid-regulated functions. 4 Jan 16

Insulin-mediated regulation of glucocorticoid-induced expression of the liver-specific gene tyrosine aminotransferase was studied in a clone of the Reuber rat hepatoma cells. Insulin inhibited dexamethasone-induced chloramphenicol acetyltransferase expression from approximately 4 kb of TAT 5' flanking sequence. The degree of this inhibition was comparable to the response of the endogenous gene. A construct of approximately 3 kbp of 5' flanking sequence exhibited no significant basal expression but retained sensitivity to glucocorticoids and to insulin inhibition of the glucocorticoid response. Results of further analysis of the insulin response in deletion constructs and constructs containing glucocorticoid responsive elements ligated to a heterologous promoter suggest that in addition to the glucocorticoid response elements a region close to the start site in the TAT promoter is necessary for insulin to inhibit glucocorticoid-mediated induction of expression.
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PMID:Insulin-mediated inhibition of the induction of tyrosine aminotransferase by dexamethasone. 135 29

To define a selective system for the study of rat tyrosine aminotransferase (TAT; EC 2.6.1.5) gene expression, we have introduced into cultured cells the selectable bacterial gene gpt linked to TAT gene flanking sequences. After integration in host cell DNA, the chimeric gene exhibits the same pattern of regulation as the TAT gene. In hepatoma cells, its expression is induced after glucocorticoid hormone treatment and repressed after fusion with fibroblasts. In fibroblasts, the chimeric gene is not expressed. The correct pattern of regulation is lost when the number of integrated copies is high. At copy number above 10, the transfected gene responds poorly to glucocorticoids in hepatoma cells. At copy number above 50, the gene is expressed in fibroblasts. Another gene present in the same construction and controlled by the SV40 early promoter and enhancer is positively regulated by glucocorticoids in hepatoma cells but not after fusion with fibroblasts. These data indicate that in hybrid cells, both TAT promoter and glucocorticoid-responsive elements are negatively regulated.
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PMID:Positive and negative regulation of a transfected chimeric tyrosine aminotransferase gene: effect of copy number. 256 29

The structural gene encoding liver-specific tyrosine aminotransferase (TAT; EC 2.6.1.5) was assigned to mouse chromosome 8 by screening a series of hybrid cell lines for retention of murine Tat-1 gene sequences by genomic Southern blotting. This assignment demonstrated that the Tat-1 structural gene was not syntenic with Tse-1, a chromosome 11-linked locus that negatively regulates TAT expression in trans (A. M. Killary and R. E. K. Fournier, Cell 38:523-534, 1984). We also showed that the fibroblast Tat-1 gene was systematically activated in hepatoma X fibroblast hybrids retaining fibroblast chromosomes 8 in the absence of chromosome 11 but was extinguished in cells retaining both fibroblast chromosomes. Thus, the TAT structural genes of both parental cell types were coordinately regulated in the intertypic hybrids, and the TAT phenotype of the cells was determined by the presence or absence of fibroblast Tse-1.
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PMID:Chromosomal assignment and trans regulation of the tyrosine aminotransferase structural gene in hepatoma hybrid cells. 287 83

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

The hormonal induction of tyrosine aminotransferase in an established line of rat hepatoma cells is enhanced by the presence of a macromolecular component of serum in the inducing medium. The addition of serum to cells previously induced in serum-free medium results in a rapid two- to threefold increase in the rate of tyrosine aminotransferase synthesis, as measured by specific radio-immunoprecipitation techniques, as well as a smaller increase in over-all protein synthesis. The stimulation of protein synthesis by serum is accompanied by an increase in the proportion of ribosomes sedimenting as polysomal aggregates. The increase in the rate of TAT synthesis is largely independent of RNA synthesis as it is insensitive to antinomycin D, suggesting that the serum acts at a site beyond gene transcription. The maximum effect of serum on TAT synthesis requires the continued presence of the hormone inducer.
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PMID:Control of tyrosine aminotransferase synthesis in tissue culture by a factor in serum. 439 Oct 23

We have used a mouse mammary tumor virus (MMTV)-infected rat hepatoma cell line as a model system for studying glucocorticoid action. These cells induce tyrosine aminotransferase and MMTV in response to the synthetic glucocorticoid, dexamethasone. The major viral antigen, a glycoprotein of 52,000 daltons (gp52), appears on the surface of infected cells in amounts which reflect the cytoplasmic content of viral RNA. Using an anti-gp52 antiserum and a fluorescence-activated cell sorter (FACS), we have selected variants which display low levels of pg52 in the presence of the hormone. Multiple cycles of enrichment for cells that fluoresce weakly in the presence of hormone have generated a population which fails to produce a detectable increase in cell surface gp52 in response to dexamethasone. This population of nonresponders and a number of independent clones derived from this population were analyzed for their ability to induce gp52 and TAT and for these presence of glucocorticoid receptors. All nonresponder clones exhibited little or no induction of either glucocorticoid-inducible marker. Two of the clones contained reduced levels of glucocrticoid receptor, while the remainder of the clones showed no detectable specific hormone binding. These results provide genetic evidence that a single class of glucocorticoid receptors is involved in the induction of both MMTV and TAT in HTC cells.
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PMID:Isolation of glucocorticoid-unresponsive rat hepatoma cells by fluorescence-activated cell sorting. 610 25

The induction of tyrosine aminotransferase by a variety of steroids was studied in cells from a hepatoma tissue culture (HTC). We have defined a class of steroids that induce TAT synthesis to a higher level than optimal inducers described earlier; these are called supra-inducers. When TAT induction is compared with the binding of the steroids to the cytoplasmic receptor or to their binding in the whole cell, a good correlation between binding in vivo of the hormone and its induction capacity can be established, whereas such a correlation was not systematically observed in vitro. A very short exposure of HTC cells to either dexamethasone or corticosterone is sufficient to induce TAT. When the inducer is removed from the culture medium a few minutes after its administration, the intracellular hormone concentration decreases very rapidly but TAT will be synthesized at its maximal rate. Thus the hormones behave as a starting signal for the optimal synthesis of the enzyme, and their presence in the culture medium is not necessary throughout the entire induction period.
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PMID:Relations between steroid-cell contact, steroid-binding and induction of tyrosine aminotransferase. 611 76


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