Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0019204 (hepatocellular carcinoma)
 71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The basic phenomena of cell fusion and hybrid cell formation are briefly described and the potential of somatic cell hybridization in studies on the expression of differentiated cellular functions is discussed. The technique of cell hybridization has been applied to two types of cellular responses to glucocorticoids. The induction of specific proteins has been investigated in hybrids of inducible cells with uninducible cells. Most studies dealt with the liver-specific enzyme tyrosine aminotransferase, whose inducibility was extinguished in the majority of the hybrids between hepatoma and nonliver cells. However, upon chromosome segregation, inducibility reappeared in some of these hybrid cells. The current ideas about cellular control of inducibility are discussed. The other major glucocorticoid-responsive system investigated in cell hybridization studies consists of lymphoid cells which are killed when exposed to the steroid. Such sensitive cells were hybridized with several types of glucocorticoid-resistant lymphoid lines, and sensitivity was found to be dominant over resistence. Hybrids between sensitive and resistant lymphoid cells, however, showed an increase in the frequency at which resistance occurred as compared to the rate observed with the wild-type parental cells. No complementation to steroid sensitivity was found in hybrids between different types of resistant cells with defects in the glucocorticoid-specific receptor system.
 ...
PMID:Somatic cell fusion in the study of glucocorticoid action. 4 Jan 17

HTC cells, an established line of rat hepatoma cells in tissue culture, provide a useful experimental model system for studying the interaction of glucocorticoids and insulin in the regulation of protein metabolism. The actions of insulin and glucocorticoids on amino acid transport and protein degradation are antagonistic in this cell line. In contrast, the actions of these two hormones are additive with regard to the induction of tyrosine aminotransferase. The addition of insulin to HTC cells previously incubated with dexamethasone causes a rapid further doubling in the cellular concentration of this enzyme. The properties of the induction by insulin differ in several respects from the induction by glucocorticoids. The former occurs immediately, without the characteristic lag observed during induction by steroids. Insulin induction of transaminase does not require concomitant RNA synthesis, and does not cause the accumulation of specific mRNA for this enzyme as do glucocorticoids. Using specific immunoprecipitation techniques, we have demonstrated that insulin stimulates a nonselective increase in the rate of total protein synthesis in HTC cells, and a selective decrease in the rate of degradation of tyrosine aminotransferase relative to total protein. Thus the induction of transaminase by insulin involves two distinct actions of the hormone, affecting both synthesis and degradation of protein.
 ...
PMID:Syneristic and antagonistic effects of glucocorticoids on insulin action. 4 Jan 18

1. Reuber H 35 hepatoma cell cultures were syncrhonized by serum depletion of the growth medium for 72 hr, which results in arrest of the cells in the G0 or G1 phase of the cell cycle. 2. Induction of tyrosine aminotransferase by dexamethasone was studied. Induction along the cell cycle varies with respect to the sensitivity of the cell towards low hormone concentration and the maximum effect elicited by the hormone. 3. Scatchard analyses of receptor- [3H]triamcinolone binding was performed in cell extracts prepared from cells at various times of G1 and S. Variations were observed in the concentration of glucocorticoid receptor as well as in the affinity of the receptor for the hormone. 4. During the latter part of the cell cycle, variations in the concentrations of the receptor could not explain the variation in enzyme induction, since the maximum rate of induction decreased while an increase in receptor activity still occurred.
 ...
PMID:Variations in some molecular events during the early phases of the reuber H 35 hepatoma cell cycle. I. Glucocorticoid induction of tyrosine aminotransferase. 4 Jun 18

We have produced somatic cell hybrids between totipotent mouse teratocarcinoma cells and rat hepatoma cells. These hybrids were tested for the expression of liver specific functions expressed in the hepatoma cell parent and for their ability to differentiate when injected into nude mice. The results of this study indicate that hybrid cell clones do not resemble either of the parental cells, since they do not produce albumin and tyrosine aminotransferase that are expressed in the rat hepatoma parent, and are incapable of forming either teratocarcinomas or hepatomas when injected in experimental animals.
 ...
PMID:Somatic cell hybrids between totipotent mouse teratocarcinoma and rat hepatoma cells. 4 96

Normal expression of a variety of hormonal effects which depend on cyclic AMP (adenosine 3':5'-monophosphate) requires the presence of glucocorticoids. Our hypothesis was that glucocorticoids control directly or indirectly the activity of cyclic-AMP-dependent protein kinase. This has been investigated in cultured hepatoma (HTC) cells in which N6,O2'-dibutyryladenosine 3':5'-monophosphate increases the activity of tyrosine transaminase only after glucocorticoid treatment. In these cells, we have determined the concentration and half-life of protein kinase, the sensitivity of this enzyme in vitro to cyclic AMP and to its thermostable protein inhibitor, the state of dissociation of protein kinase holoenzyme in vivo and its sensitivity, in the intact cell, to dibutyryladenosine 3':5'-monophosphate and to the inhibitor diamide, and we have also determined the concentration of endogenous thermostable protein inhibitor of protein kinase. None of these parameters were influenced by glucocorticoids under conditions where these hormones stimulate the activity of tyrosine transaminase and restore sensitivity to dibutyryladenosine 3':5'-monophosphate. It is concluded that the permissive action of glucocorticoids probably results from a control of cyclic-AMP-dependent processes exerted at a level beyond the protein kinase system.
 ...
PMID:Activity of protein kinase dependent on adenosine 3':5'-monophosphate and of its thermostable protein inhibitor in rat hepatoma (HTC) cells. Unlikely role in the permissive action of glucocorticoids. 19 14

We have studied glucagon induction of enzymes, adenosine 3', 5'-monophosphate concentrations, and glucose repression in Morris 9618A hepatoma and in the liver of rats fed, for periods of up to 5 weeks, a solid diet containing 2-acetylaminofluorene or 3'-methyl-4-dimethylaminoazobenzene. While the basal levels of the enzymes serine dehydratase and tyrosine aminotransferase were the same as those found in control rats, their response to glucagon was reduced in experimental animals with or without tumors. However, the basal or glucagon-stimulated levels of adenosine 3', 5'-monophosphate in the liver of rats given the carcinogens were not changed. In Morris 9618A hepatoma, these parameters were, likewise, comparable to those in control animals. When glucose was administered to carcinogen-treated or tumor-bearing rats that had received a single dose of glucagon, there was no suppression of the increase in activity of serine dehydratase and tyrosine aminotransferase observed after glucagon treatment alone. The loss of glucose repression was seen already at 2 to 3 weeks following initiation of the carcinogenic diets. As previous studies had established for normal liver, the hormone-induced high levels of adenosine 3',5'-monophosphate remained unchanged also in Morris 9618A hepatoma and in rats given carcinogen. These results indicate that alterations in enzyme induction during chemical carcinogenesis are not the consequence of changes in adenosine 3',5'-monophosphate levels caused by carcinogens. The early disappearance of the glucose effect, which persists in slow-growing hepatomas, may be an expression of interference by carcinogens with the translation apparatus of the hepatic cell.
 ...
PMID:Induction of enzymes by glucagon, glucose repression, adenosine 3',5'-monophosphate concentration during carcinogenesis and in Morris 6918A hepatoma. 23 92

Anucleate HTC cells have been used to determine the importance of the nucleus in the regulation of the intracellular levels of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells. In the absence of the nucleus, neither the induction of the enzyme by dexamethasone nor its deinduction upon removal of the hormone occurs. Degradation of the enzyme takes place when protein synthesis is inhibited in anucleates by cycloheximide. Therefore, the maintenance of induced levels of enzyme activity after dexamethasone withdrawal from pre-induced anucleates suggest that the nucleus is required for the inactivation of the TAT mRNA.
 ...
PMID:Analysis of the induction and deinduction of tyrosine aminotransferase in enucleated HTC cells. 23 57

Reexamination of the effects of actinomycin D (AMD) on the intracellular level and rate of synthesis of tyrosine aminotransferase (TAT) in hepatoma tissue culture (HTC) cells reveals that much apparent controversy can be resolved with acknowledgment of the multi-faceted nature of this inhibitor's action. AMD can slow overall protein synthesis and inhibit the degradation of both TAT and its mRNA as well as block the synthesis of RNA. The extent of these secondary actions of the inhibitor depend somewhat upon the growth condition of the cells. The effects of cordycepin (3'-deoxyadenosine) on the metabolism of TAT and its mRNA are also complex, but differ in several respects from those of AMD.
 ...
PMID:"Superinduction" of tyrosine aminotransferase by actinomycin D: a reevaluation. 23 35

The specific rate of synthesis of tyrosine aminotransferase (EC 2.6.1.5; L-tyrosine:2-oxoglutarate aminotransferase) is used as a measure of the level of functional, cytoplasmic, tyrosine aminotransferase-specific mRNA in cultured rat hepatoma cells. An analysis of the kinetics of change in this rate after the addition or withdrawal of glucocorticosteroids sets an upper limit on the half-life of the enzyme-specific mRNA of 1-1.5 hr, whether or not steroid is present. The inactivation rate of the enzyme mRNA is independent of the growth condition of the cells, occuring equally rapidly in the presence or absence of serum or insulin, both of which induce tyrosine aminotransferase in these cells. The implications of these results for the mechanism of steroid induction are discussed.
 ...
PMID:Kinetics of steroid induction and deinduction of tyrosine aminotransferase synthesis in cultured hepatoma cells. 23 68

A variety of 6- and 8-substituted analogs of cAMP (cyclic adenosine 3:5-monophosphate) have been tested for their ability to increase activity of tyrosine aminotransferase (EC 2.6.1.5) in cultured Reuber H35 hepatoma cells. Some analogs, particularly the 8-thio-substituted ones, produced effects approximately equivalent to those generated by N-6, O2'-dibutyryl cAMP. In contrast, cAMP and its O-2-monobutyryl derivative were relatively ineffective even at very high concentrations, whereas three other analogs actually depressed the activity of the aminotransferase. Changes in enzyme activity generated by the various analogs were paralleled closely by changes in the relative rate of aminotransferase synthesis. An excellent correlation was found to exist between the ability of any given analog to influence the activity of tyrosine aminotransferase and that of phosphoenolpyruvate carboxykinase (EC 4.1.1.32). A similar correlation was found to exist between the ability of various analogs to evelate the activity of these enzymes and to inhibit reversibly the growth of H35 cells. Only one of five inhibitors of cAMP phosphodiesterase activity tested produce any increase in aminotransferase activity when added alone. All of the 6- and 8-substituted analogs tested, including noniducers, stimulated f1 histone phosphorylation in crude rat liver extracts with approximately equal potencies. On the other hand, dibutyryl cAMP was only a weak activator of protein kinase in vitro, even though it is a potent enzyme inducer. A possible resolution of this apparent discrepancy has been provided by preliminary analyses of site-specific f1 histone phosphorylation in whole cells. Only compounds active as aminotransferase inducers are capable of stimulating phosphorylation of the serine-37 residue of endogenous f1 histone (3- to 10-fold).
 ...
PMID:Effects of 6- and 8-substituted analogs of adenosine 3':5'-monophosphate on phosphoenolpyruvate carboxykinase and tyrosine aminotransferase in hepatoma cell cultures. 23 87


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>