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)

The human apolipoproteins are secretory proteins some of which have been shown to undergo proteolytic processing and post-translational addition of carbohydrate. Apolipoprotein A-I (apo-A-I), the predominant protein associated with high density lipoproteins, undergoes co-translational proteolytic processing as well as post-translational conversion of proapo-A-I to mature apo-A-I following cellular secretion. Utilizing the human hepatoma cell line HEP-G2, we have established that, in addition to proteolytic processing, secreted nascent apo-A-I is acylated with palmitate. Uniformly labeled [14C]palmitate and [1-14C]palmitate were each incorporated into apo-A-I when analyzed by sodium dodecyl sulfate gel electrophoresis and autoradiography. The acylation of apo-A-I with palmitate was confirmed by immunoprecipitation and gas chromatography/mass spectrometry. Hydroxylamine treatment resulted in the deacylation of apo-A-I. Although three of the apo-A-I isoforms analyzed by two-dimensional gel electrophoresis were shown to contain radio-labeled palmitate, 80% of acylated apo-A-I was in the proapolipoprotein A-I isoform. [14C]Oleate was not incorporated in secreted apo-A-I, indicating the specificity of the acylation of apo-A-I. Incubation of [14C] palmitate-acylated apo-A-I in serum and plasma under conditions in which proapo-A-I is proteolytically cleaved to mature apo-A-I did not result in deacylation. These data establish that fatty acid acylation occurs in human secretory proteins in addition to the previously reported acylation of cellular membrane proteins. These results suggest that the covalent linkage of lipids to apolipoproteins may play a critical role in apolipoprotein and lipoprotein metabolism.
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PMID:Human apolipoprotein A-I. Post-translational modification by fatty acid acylation. 300 8

Metabolic cooperation between cells from three human hepatoma cell lines was studied by the clonogenic method and by autoradiography. It was found that human HGPRT+/HGPRT- SK-HEP-1 cells only, showed a metabolic cooperation capacity that was inhibited by tumour promoters 12-O-tetradecanoylphorbol-13-acetate (TPA) and phenobarbital, and was not inhibited by the non-promoter 4-O-methyl TPA, provided suitable experimental conditions (short exposure times) were used. This biological system might be the basis of a new in vitro short-term screening test for potential tumour-promoting chemicals.
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PMID:Effects of tumour promoters on metabolic cooperation between human hepatoma cells. 301 43

The potential of fibrate drugs to induce peroxisomal proliferation in human liver cells was evaluated in athymic nude mice transplanted with human hepatoma cells and treated by clofibrate in vivo as well as in cultured human hepatoma cells in the presence of fibrate drugs added to the culture medium. Clofibrate did not induce peroxisomal activities and neither acted as a peroxisomal proliferator in human PLC/PRF/5 or SK-HEP-1 heterotransplants under conditions of induction of peroxisomal activities in the host rodent liver. Similarly, clofibric acid or bezafibrate did not induce peroxisomal activities in cultured human PLC/PRF/5 or SK-HEP-1 cells under conditions of induction of peroxisomal activities in cultured primary rat liver cells. The lack of response of the human cells to peroxisomal proliferators of the fibrate type may indicate a species specificity with respect to induction of peroxisomal activities by xenobiotic peroxisomal proliferators.
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PMID:Clofibrate does not induce peroxisomal proliferation in human hepatoma cell lines PLC/PRF/5 and SK-HEP-1. 303 May 38

Previous studies have demonstrated that mouse embryonal carcinoma (EC) cells produce at least two growth factors: one related to platelet-derived growth factor (PDGF) and another related to basic fibroblast growth factor (FGFb). Since human EC cell lines are being used with increased frequency, the current study examined whether human EC cells produce growth factors, in particular those produced by mouse EC cells. In this study, it was determined that the human EC cell line NT2/D1 produces a heat-labile heparin-binding growth factor that behaves like FGF in a bioassay. Three additional criteria suggest that this factor is closely related or identical to FGFb. The factor from NT2/D1 EC cells, bovine FGFb and FGFb produced by the human hepatoma cell line SK-HEP-1 elute from heparin at similar salt concentrations. The factor produced by NT2/D1 EC cells exhibits a thermal stability curve that is nearly identical to those for bovine FGFb and FGFb from SK-HEP-1 cells. Lastly, NT2/D1 and SK-HEP-1 cells express transcripts of the same size that hybridize with a cDNA probe for human FGFb. In the course of these studies it was determined that NT2/D1 EC cells also express several transcripts that hybridize with a cDNA probe for the human PDGF A-chain. Thus, our findings suggest that the pattern of growth factor production by human and mouse EC cells is evolutionarily conserved.
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PMID:Production of growth factors related to fibroblast growth factor and platelet-derived growth factor by human embryonal carcinoma cells. 320 87

Previous studies have demonstrated differences in the size of insulin receptor subunits in brain and adipocytes that appear to involve variations in glycosylation of the proteins. In this report, we examined the degree of homology in the protein backbones of insulin receptors in both tissues by peptide mapping and compared the mRNAs encoding the receptors by Northern blot analysis. Photoaffinity-labeled insulin receptors from rat brain and adipocytes were deglycosylated and then subjected to partial proteolysis by five different enzymes with differing substrate specificities. The intact receptors and their proteolytic fragments were analyzed by electrophoresis and autoradiography. Each enzyme yielded a unique pattern of fragments ranging from 70 to 11 kDa. In all cases, there was a striking similarity in the peptide maps generated from insulin receptors in brain and adipocytes. Northern hybridization experiments were carried out using poly(A)+ RNA from rat brain, rat adipocytes, and human hepatocarcinoma (HEP G2) cells. In rat brain, two bands of 9.5 and 7.4 kb were detected and, in rat adipocytes, the same two bands were observed. The two mRNA bands observed in rat tissues represented only two of the five mRNA species seen in human HEP G2 cells. The results indicate that the protein domains and the mRNAs encoding of insulin receptors in brain and adipocytes are very similar, if not identical.
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PMID:Peptide mapping on Northern blot analyses of insulin receptors in brain and adipocytes. 328 25

A new cell line derived from a woodchuck hepatitis surface antigen-positive woodchuck hepatocellular carcinoma has been established and named T3-HEP-W1. This new cell line was established directly from a primary woodchuck hepatocellular carcinoma. Adaptation of the cells to the in vitro culture condition was completed after 3 months, with the doubling time of 24 hr. The morphologic features of the cell by light microscopy were of an epithelial type. The modal chromosome number was 100. Ornithine and tyrosine aminotransferase activities were detected. Production of albumin was negative. Integration of woodchuck hepatitis virus DNA was demonstrated by Southern blot analysis, although the secretion of woodchuck hepatitis surface antigen was not detected. T3-HEP-W1 is quite different from the previously reported WH257GE10 cell line and provides another in vitro model for the study of human hepatocellular carcinoma related to hepatitis B virus.
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PMID:Establishment of a new cell line from a woodchuck hepatocellular carcinoma. 333 96

A lipoprotein-induced resistance to the action of insulin has been postulated. To test this hypothesis, cultured rat-derived hepatoma cells, designated FAO, and human-derived hepatoma cells, designated HEP-G2, were incubated for 20 h in the presence or absence of lipoprotein; specific 125I-insulin receptor binding and labeled glucose incorporation into glycogen were then measured. Very low density lipoproteins (d less than 1.006 g/ml) in physiologic (0.5 mg/ml) or pathophysiologic (5 mg/ml) concentrations did not modify insulin receptor binding of FAO or HEP-G2 cells. This was true for very low density lipoproteins derived from normal human, diabetic human, and streptozotocin-diabetic rat plasma. Low density lipoproteins (d = 1.019 - 1.063 g/ml) isolated from normal human plasma similarly failed to modify insulin receptor binding. Concerning insulin action, the different very low density lipoprotein preparations did not modulate either basal or insulin-stimulated glucose incorporation into glycogen of the cells. Thus, very low density lipoproteins and low density lipoproteins did not induce insulin resistance in cultured hepatoma cells either at the insulin receptor level or at the post-receptor level.
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PMID:Lack of a lipoprotein-induced insulin resistance in hepatoma cells in culture. 352 46

We investigated the biosynthesis of the human insulin receptor in IM-9 lymphocytes and HEP-G2 hepatoma cells. Cells were first pulse labeled for 15 min with [35S]methionine and then chased for up to 4 h. At each time, the cells were solubilized in 1% Triton X-100; the insulin receptor was immunoprecipitated and then analyzed with sodium dodecyl sulfate-polyacrylamide gel electrophoresis (6%) and fluorography. At 15 min, a major precursor protein of 190,000 Mr was precipitated. During the chase period, two smaller proteins became apparent, which evolved into two major species of 130,000 and 95,000 Mr, the mature alpha- and beta-subunits, respectively. When IM-9 cells were trypsinized after pulse chase, the alpha- and beta-subunits were completely digested, whereas the 190,000-Mr precursor was unaffected. 125I-surface labeling of cells, followed by immunoprecipitation, revealed the presence of only the alpha- and beta-subunits, indicating that only these two species were on the cell surface. To study this biosynthetic pathway, several inhibitors were used (tunicamycin, monensin, and swainsonine). These inhibitors revealed the following. The receptor is first synthesized as a 170,000-Mr protein that is cotranslationally N-glycosylated to yield a high-mannose 190,000-Mr precursor. This precursor is rapidly transported from the endoplasmic reticulum to the Golgi apparatus where it is cleaved into two subunits of 120,000 Mr (alpha) and 90,000 Mr (beta). These subunits then increase in molecular weight by processing of the high-mannose oligosaccharides to the low-mannose complex type. The two subunits then migrate to the cell surface where they function to transmit the insulin signal.
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PMID:Biosynthesis and processing of the human insulin receptor. 372 Oct 67

Insulin and the insulinlike growth factors (IGF-I and IGF-II) are members of a family of hormones that regulate the metabolism and growth of many tissues. Cultured HEP-G2 cells (a minimal deviation human hepatoma) have insulin receptors and respond to insulin by increasing their glycogen metabolism. In the present study with HEP-G2 cells, we used 125I-labeled insulin, IGF-I, and IGF-II to identify distinct receptors for each hormone by competition-inhibition studies. Unlabeled insulin was able to inhibit 125I-IGF-I binding but not 125I-IGF-II binding. A mouse monoclonal antibody to the human insulin receptor that inhibits insulin binding and blocks insulin action inhibited 75% of 125I-insulin binding, but inhibited neither 125I-IGF-I nor 125I-IGF-II binding. When glycogen metabolism was studied, insulin stimulated [3H]glucose incorporation into glycogen in a biphasic manner; one phase that was 20-30% of the maximal response occurred over 1-100 pM, and the other phase occurred over 100 pM-100 nM. The anti-receptor monoclonal antibody inhibited the first phase of insulin stimulation but not the second. Both IGF-I and IGF-II stimulated [3H]glucose incorporation over the range of 10 pM-10 nM; IGF-I was three to fivefold more potent. The monoclonal antibody, however, was without effect on IGF regulation of glycogen metabolism. Therefore, these studies indicate that insulin as well as the IGFs at physiological concentrations regulate glycogen metabolism in HEP-G2 cells. Moreover, this regulation of glycogen metabolism is mediated by both the insulin receptor and the IGF receptors.
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PMID:Dual regulation of glycogen metabolism by insulin and insulin-like growth factors in human hepatoma cells (HEP-G2). Analysis with an anti-receptor monoclonal antibody. 609 May 2

Insulin-like growth factors (IGF's) circulate in blood complexed to specific carrier proteins. The BRL 3A and BRL 3A2 rat liver cell lines secrete a 30,000-50,000 mol wt IGF carrier protein. Since the liver parenchymal cell is a likely source of IGF carrier protein synthesis, we have evaluated medium conditioned by three human hepatocellular carcinoma- or hepatoblastoma-derived cell lines for the presence of IGF carrier protein. The HEP G2 and the HEP 3B, but not the PLC/PRF/5, cell lines secrete a specific IGF carrier protein(s) into serum-free medium. This carrier protein is specific for IGF molecules. Multiplication-stimulating activity, IGF I, and IGF II were equipotent in competing for the binding of [125I]multiplication-stimulating activity to HEP G2 medium. The HEP G2 IGF carrier protein is trypsin sensitive, acid stabile, and does not contain a glycoprotein moiety. It has a molecular size of 30,000-50,000, as assessed by Sephadex G-200 gel filtration. These studies suggest that the HEP G2 cell line is a useful model to study the synthesis and secretion of human IGF carrier protein.
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PMID:Demonstration that a human hepatoma cell line produces a specific insulin-like growth factor carrier protein. 618 61


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