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)

c-jun mRNA levels were increased in rat hepatoma cells (H4-II-E-C3) when exposed to hypotonic medium (205 mosmol/l) with a maximal induction observed after 1 h of hypotonic exposure. At this time point an approximate 5-fold increase in c-jun expression could be detected in relation to normotonic control incubations (305 mosmol/l). Hypertonic exposure (405 mosmol/l) had only a slight effect on c-jun expression. In contrast to the increased c-jun mRNA levels under hypotonic conditions, expression of the c-fos proto-oncogene was unaffected by changes in the osmolarity. The hypotonicity-induced increase in c-jun expression was also detectable in the presence of a protein kinase C (PKC) inhibitor. This indicates that PKC is not involved in the signal transduction pathway leading to c-jun expression upon hypotonic cell swelling in these cells.
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PMID:Increase of c-jun mRNA upon hypo-osmotic cell swelling of rat hepatoma cells. 813 38

Apoptotic cell death plays a major role in the regulation of cell growth and this process may be activated by different agents through various pathways. The present study aimed to elucidated the mechanism of apoptosis caused by transforming growth factor beta 1 (TGF-beta 1) in human hepatoma cells. Several biological parameters which were reported to be crucial in the induction of programmed cell death in other experimental systems were measured. We found that TGF-beta 1-induced cell death is independent of cytosolic calcium and protein kinase C. Insulin and tumor promotor can rescue hepatoma cells from apoptosis, but the effect is time-dependent. Our results highlight that different apoptotic signal transduction pathways exist in different cell types. Apoptosis induced by TGF-beta 1 provides a good model for the understanding of cell death and the development of new anti-cancer drugs. Apoptotic cell death (apoptosis or programmed cell death) in normal tissue is a biological phenomenon that maintains hemostasis of systems of the body under physiological conditions. The features of apoptosis include condensation of chromatin, blebbing of the cell surface, transient increase in buoyant density and fragmentation of chromatin by a specific endonuclease.
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PMID:Characterization of apoptosis induced by transforming growth factor beta 1 in human hepatoma cells. 816 42

Transcription of the cytoskeletal beta-actin gene is rapidly induced by phorbol 12-myristate 13-acetate (PMA) and the calcium ionophore, A23187, in cultured H4IIE hepatoma (H4) cells. PMA directly activates protein kinase C (PKC) and activation of PKC is necessary for the cellular actions of PMA, including induction of beta-actin gene transcription. In the present study, we determined the DNA sequence requirements for induction of the beta-actin gene by PMA and A23187. Constructs containing progressive deletions of normal and mutated human beta-actin 5' sequences fused to the reporter gene, bacterial chloramphenicol acetyltransferase, were analysed in transient transfections of H4 cells. We delineated the PMA response DNA element of the human beta-actin gene to the proximal CCArGG box (-62 to -53) in the 5' flanking region. In contrast, A23187 did not induce expression of transfected gene constructs containing this CCArGG box. Additionally, we demonstrated that CCArGG boxes from two other PMA-induced genes in H4 cells, c-fos and gamma-actin, could confer PMA inducibility to a heterologous promoter. This CCArGG box specifically interacts with one or more proteins present in nuclear extracts of H4 cells. These results indicate that in cultured cells, PMA-dependent induction of the beta-actin gene is mediated through the proximal CCArGG box. This suggests that the CCArGG box is a target for PKC action and may be involved in the control of other PKC regulated genes.
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PMID:Identification of beta-actin sequences necessary for induction by phorbol esters and calcium ionophores. 818 67

Chronic infection with hepatitis B virus (HBV) is accompanied by an increasing risk of developing hepatocellular carcinoma. There are indications that the HBx protein of HBV is involved in the process of tumour formation. HBx also transactivates several transcription factor binding sites. Recently, we reported that HBx can use a tumour promotor pathway for transactivation. In particular, we found that transactivation of the binding motif for transcription factor AP-1 (JUN/FOS) by HBx is dependent on functional protein kinase C (PKC), as indicated by abolition of the transcriptional stimulation following downregulation or inhibition of the enzyme. Moreover, HBx activates PKC, probably via increasing the endogenous PKC activator sn-1,2-diacylglycerol (DAG). Here we extend these data and report on the time course of PKC activation. We found that activation of PKC by HBx is transient and differs from activation of PKC by the ras oncogene product or phorbol ester in that it does not lead to rapid downregulation of the enzyme subsequent to the activation. Moreover, we provide evidence that an increase in cellular DAG is observable not only as an early event in response to HBx but also in cell lines transformed after transfection with HBV DNA and stably expressing HBx. Besides its important role in the regulation of cellular genes, PKC is also the intracellular receptor for tumour-promoting agents and an activator of proto-oncogenes, suggesting that our observations might provide an explanation for the oncogenic properties of HBx.
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PMID:The hepatitis B virus transactivator HBx causes elevation of diacylglycerol and activation of protein kinase C. 821 Jul 15

The purification and identification of human prolactin (hPRL) had been delayed, compared with other pituitary hormones, until the determination of total amino acid sequence of hPRL in 1977. A full-length cDNA for the hPRL receptor was identified from hepatoma and breast cancer cell lines in 1989. Subsequent identification of cDNAs for PRL receptor of several species revealed that molecular size of PRL receptors could be classified into three forms, i.e., long, short and intermediate, according to the length of intracellular domain. The mechanism of post-receptor signal transduction has not been clarified yet. However, protein kinase C may be involved in this process. Further studies are necessary to investigate the relationship between molecular size of PRL receptor and postreceptor events.
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PMID:[Action mechanism of pituitary hormones--receptor and signal transduction--prolactin]. 825 31

It is well known that interferon-gamma (IFN-gamma; type II) potentiates various responses of human tumor necrosis factor (TNF) in a wide variety of cells and that this potentiation is accompanied by the up-regulation of TNF receptor synthesis. In the present studies we examined the regulation of TNF receptors by type I and type II IFNs in a hepatocellular carcinoma cell line, HEP G2. Exposure of these cells to IFN-gamma led to a decrease in TNF receptor number (4029 vs. 2719 sites/cell) without any change in the receptor affinity (0.96 nM vs. 1.1 nM). The effect was time and dose-dependent. Like IFN-gamma, IFN-alpha and IFN-beta (type I) down-modulated the TNF receptors on these cells. The effect of IFNs on the TNF receptors was inhibited by staurosporin, a protein kinase C (PK-C) inhibitor. Furthermore, by the use of receptor-specific antibodies, we found that the IFN-dependent decrease was primarily due to the p60 form of the TNF receptor. Our results presented are the first to demonstrate that IFNs can also down-modulate TNF receptors in certain cells and that this effect is mediated through PK-C.
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PMID:Both type I and type II interferons down-regulate human tumor necrosis factor receptors in human hepatocellular carcinoma cell line Hep G2. Role of protein kinase C. 827 22

Teleocidin, a phorbol ester-type tumor promoter, inhibits cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in PLC/PRF/5 hepatoma cells. These inhibitory effects of teleocidin were observed even after a prolonged exposure of the hepatoma cells to this promoter, suggesting the presence of down-regulation-resistant protein kinase C in this hepatoma cell line. Column chromatography of cytosolic fractions showed three separate peaks of protein kinase C activity, two being down-regulation-sensitive while one was down-regulation-resistant. This down-regulation-resistant PKC is suggested to be responsible for the inhibitory effect of teleocidin on cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin.
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PMID:Involvement of down-regulation-resistant protein kinase C in teleocidin inhibition of cell proliferation and calcium mobilization induced by epidermal growth factor and vasopressin in human hepatoma cells. 839 71

Rat ascites hepatoma (AH) cells (10(6) cells/head) inoculated intraperitoneally into rats had host-killing ability (malignancy) in the order AH66F > AH44 > AH13 > AH7974 > AH109A > AH66 > AH130. The life span of the rats after inoculation closely correlated with the activity of cyclic AMP-dependent protein kinase (protein kinase A) in the tumor cells but not the activity of Ca2+/phospholipid-dependent protein kinase (protein kinase C). N-[2-[N-[3-(4-chlorophenyl)-1-methyl-2-propenyl]amino]ethyl]-5- isoquinoline-sulfonamide (H-87), a potent, selective inhibitor of protein kinase A, inhibited in vitro growth of these hepatoma cells with a similar potency and, intraperitoneally injected, prolonged the lives of rats bearing less malignant AH66 cells (with high protein kinase A activity) but did not affect the life span of rats bearing highly malignant AH66F cells (with low protein kinase A activity). On the other hand N-(2-methylpiperazyl)-5-isoquinolinesulfonamide (H-7), an inhibitor of protein kinase C, inhibited AH66F cells more than AH66 cells, but did not influence the life span of rats bearing either hepatoma. From these results it is deduced that protein kinase A may be important in the regulation of malignancy and in vivo proliferation of AH cells.
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PMID:Reverse relationship between malignancy and cyclic AMP-dependent protein kinase activity in Yoshida rat ascites hepatomas. 840 89

1. The regulation of the increase in the cytosolic calcium concentration ([Ca2+]c) induced by extracellular ATP in AS-30D hepatoma cells was studied. 2. Homologous desensitization involving the refilling of intracellular calcium pools and the participation of protein kinase C was found. 3. Isoproterenol, forskolin and dibutyryl-cyclic AMP also induced an increase in [Ca2+]c. 4. Interestingly, synergism was found for isoproterenol or forskolin and ATP. 5. The results suggest that there are two pathways for mobilizing [Ca2+]c in AS-30D hepatoma cells; one is activated by ATP receptors and the other by cyclic AMP.
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PMID:Modulation of the ATP induced [Ca2+]c increase in AS-30D hepatoma cells. 840 51

Choline deficiency, via deprivation of labile methyl groups, is associated with a greatly increased incidence of hepatocarcinoma in experimental animals. This dietary deficiency also causes fatty liver, because choline is needed for hepatic secretion of lipoproteins. We hypothesized that fatty liver might be associated with the accumulation of 1,2-sn-diradylglycerol and subsequent activation of protein kinase C. Several lines of evidence indicate that cancers might develop secondary to abnormalities in protein kinase C-mediated signal transduction. We observed that rats fed a choline-deficient diet for 1, 6, or 27 weeks had increased hepatic concentrations of 1,2-diradylglycerol. At 1 and 6 weeks, hepatic plasma membrane from choline-deficient rats had increased concentrations of 1,2-sn-diacylglycerol and 1-alkyl, 2-acylglycerol, with the latter accounting for 20-26% of membrane 1,2-sn-diradylglycerol (as compared with only 2-5% in controls). Protein kinase C activity was increased in hepatic plasma membrane at 1 week of choline deficiency. By Western blotting there was an increase in the amount of protein kinase C zeta and a decrease in the amount of protein kinase C delta in liver at 1 week. By 6 weeks of choline deficiency, hepatic plasma membrane and cytosolic protein kinase C (PKC) activities were increased significantly, with increased amounts of hepatic plasma membrane protein kinase C alpha, and delta detected by Western blotting. Glycogen synthase activity in liver was diminished after 1 week of choline deficiency; this enzyme is inhibited by PKC-mediated phosphorylation. We suggest that choline deficiency perturbed PKC-mediated transmembrane signaling within liver and that this contributed to the development of hepatic cancer in these animals.
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PMID:Accumulation of 1,2-sn-diradylglycerol with increased membrane-associated protein kinase C may be the mechanism for spontaneous hepatocarcinogenesis in choline-deficient rats. 842 Sep 80


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