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)

Human S-protein is a serum glycoprotein that binds and inhibits the activated complement complex, mediates coagulation through interaction with antithrombin III and plasminogen activator inhibitor I, and also functions as a cell adhesion protein through interactions with extracellular matrix and cell plasma membranes. A full length cDNA clone for human S-protein was isolated from a lambda gt11 cDNA library of mRNA from the HepG2 hepatocellular carcinoma cell line using mixed oligonucleotide sequences predicted from the amino-terminal amino acid sequence of human S-protein. The cDNA clone in lambda was subcloned into pUC18 for Southern and Northern blot experiments. Hybridization with radiolabeled human S-protein cDNA revealed a single copy gene encoding S-protein in human and mouse genomic DNA. In addition, the S-protein gene was detected in monkey, rat, dog, cow and rabbit genomic DNA. A 1.7 Kb mRNA for S-protein was detected in RNA from human liver and from the PLC/PRF5 human hepatoma cell line. No S-protein mRNA was detected in mRNA from human lung, placenta, or leukocytes or in total RNA from cultured human embryonal rhabdomyosarcoma (RD cell line) or cultured human fibroblasts from embryonic lung (IMR90 cell line) and neonatal foreskin. A 1.6 Kb mRNA for S-protein was detected in mRNA from mouse liver and brain. No S-protein mRNA was detected in mRNA from mouse skeletal muscle, kidney, heart or testis.
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PMID:Human and mouse S-protein mRNA detected in northern blot experiments and evidence for the gene encoding S-protein in mammals by Southern blot analysis. 200 76

Epidermal growth factor (EGF)-induced increases in cytosolic Ca2+ and inositol polyphosphate production were compared in a human hepatocellular carcinoma-derived cell line, PLC/PRF/5, and in an EGF receptor-overexpressing subline, NPLC/PRF/5. Formation of these second messengers was correlated to EGF receptor display at the cell surface by monitoring ligand-induced EGF receptor down-regulation. Both cell lines exhibited a strikingly similar cytosolic Ca2+ increase upon exposure to EGF. The initial inositol phosphate responses were also similar in the two cell lines; inositol 1,4,5-trisphosphate increased within 10-15 s and returned to prestimulatory values after 2 min in both cell lines, while inositol tetrakisphosphate and inositol 1,3,4-trisphosphate were elevated after a 2-min exposure to EGF. At later times the responses were markedly different; NPLC/PRF/5 cells exhibited prolonged production of inositol 1,3,4-trisphosphate and inositol tetrakisphosphate (maximum at 1-3 h) but PLC/PRF/5 cells showed decreased levels of these isomers after 10 min and a return to basal values by 1 h. Exposure of PLC/PRF/5 cells to EGF caused a progressive decrease in the amount of EGF receptor at the cell surface whereas such treatment did not change the surface receptor levels in NPLC/PRF/5 cells. Kinetic analysis of EGF receptor down-regulation showed that receptor internalization was rapid enough to account for the transient nature of the inositol phosphate response in PLC/PRF/5 cells. Thus, the divergent patterns of signaling exhibited by the two cell lines may reflect differences in the efficiency of EGF-induced down-regulation of surface receptors.
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PMID:EGF receptor down-regulation attenuates ligand-induced second messenger formation. 215 64

To study the mechanism of induction of human C-reactive protein (CRP) gene expression, we have utilized an in vitro liver cell system to analyze the cis-acting DNA sequences located within the 5'-flanking region of human CRP gene. Stable transfection of human hepatoma cells, PLC/PRF/5, by a CRP gene construct containing the 1 kilobase pair of upstream sequence of the CRP gene demonstrated that this region contained the inducible element(s) which regulated human CRP gene transcription. Dissection of this region by 5', 3' and internal deletion constructs of upstream region of the CRP gene fused to a reporter gene, chloramphenicol acetyl transferase, indicated the presence of two inducible elements located proximal to the site of initiation of transcription, two constitutive enhancer-like elements located distal to the promoter, and a negative regulatory region located between the two inducible elements. We had previously shown that a protein factor from monocytes or HTLV1-infected T-cells, was responsible for CRP induction in hepatoma cells. We have found this factor to be synonymous with interleukin-6. By stable and transient transfection assays in hepatoma cells, recombinant interleukin-6 alone was sufficient to activate both inducible elements.
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PMID:cis-acting elements responsible for interleukin-6 inducible C-reactive protein gene expression. 215 96

There is little information regarding the molecular mechanisms of hepatocarcinogenesis. We studied the p53 gene at the DNA, RNA, and protein level in seven human hepatocellular carcinoma (HCC)-derived cell lines; six of seven showed p53 abnormalities. By Southern blotting, the p53 gene was found to be partially deleted in Hep 3B and rearranged in SK-HEP-1 cells. Transcripts of the p53 gene were undetectable in Hep 3B as well as in FOCUS cells that had no apparent deletion or rearrangement of the p53 gene. Immunoprecipitation after [35S]methionine labeling of HCC cells demonstrated that p53 protein was absent in Hep 3B and FOCUS and reduced in concentration in PLC/PRF/5 cells. p53 synthesized by Mahlavu cells showed a slower migration on SDS/polyacrylamide gels suggesting it was an abnormal protein. In Huh7 cells, p53 protein had a prolonged half-life leading to its accumulation in the nuclei; increased levels of p53 protein were also found by immunoblotting. The p53 gene and its expression appeared to be unaltered in the hepatoblastoma-derived Hep G2 cell line. We found that the loss of p53 expression did not occur as a late in vitro event in the FOCUS cell line because p53 protein was also nondetectable at an early passage. We conclude that the loss of p53 expression or the presence of abnormal forms of the protein are frequently associated with HCC cell lines. These observations suggest that alterations in p53 may be important events in the transformation of hepatocytes to the malignant phenotype.
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PMID:Abnormal structure and expression of p53 gene in human hepatocellular carcinoma. 215 27

Resorthiomycin, a novel antitumor antibiotic, was isolated from the fermentation broth of a strain of Streptomyces collinus by ethyl acetate extraction, silica gel chromatography and HPLC. Resorthiomycin exhibited an in vitro cytotoxic activity against mouse leukemia L5178Y cells (IC50, 15.5 micrograms/ml) and also inhibited the clonogenic activity of a multidrug-resistant mutant of human hepatoma PLC/PRF/5 cells to a greater extent than that of the parental cells. On the other hand, this antibiotic does not possess any antibacterial or antifungal activity.
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PMID:Resorthiomycin, a novel antitumor antibiotic. I. Taxonomy, isolation and biological activity. 215 95

The mRNAs of transiently expressed cytokine genes contain AUUUA-rich sequences in the 3' untranslated regions. In order to examine whether the AU-specific endoribonuclease V (EC 3.1.27.8) described previously by us transinactivates those mRNA species, we introduced a 51-nucleotide ATTTA sequence from tumor necrosis factor into the 3' untranslated region of beta-globin gene. Transcripts of that construct, synthesized in vitro, were prone to endoribonuclease V digestion at those AU-rich sequences. Stimulation of human macrophages with lipopolysaccharide resulted in a shift of the association state of the enzyme from the nuclear matrix-associated to the free form. This shift was strongly prevented by the hepatitis B surface antigen (HBsAg) and more weakly by hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region. HBsAg and, to a lesser extent, hepatitis B nucleocapsid antigen and hepatitis B antigen of the X region inhibited the release of alpha interferon, tumor necrosis factor alpha, and granulocyte-macrophage colony stimulating factor, while it had no effect on interleukin-1 production from stimulated macrophages. Using the human hepatoma cell line PLC/PRF/5, we provide further experimental evidence that endoribonuclease V acts in trans as a posttranscriptional inactivator for nuclear matrix-associated cytokine transcripts. These results suggest that those cytokine transcripts which contain reiterated (overlapping) AUUUA sequences are degraded by nuclear matrix-associated endoribonuclease V. This degradation was comparably high in cells incubated with HBsAg or cells which produced this antigen.
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PMID:Immunosuppressive function of hepatitis B antigens in vitro: role of endoribonuclease V as one potential trans inactivator for cytokines in macrophages and human hepatoma cells. 215 63

The transcriptional activities of the four hepatitis B virus promoters were compared in three differentiated hepatoma cell lines, HepG2, Hep3B, and PLC/PRF/5; a dedifferentiated subline of HepG2, HepG2.1; a human cervical carcinoma cell line, HeLa S3; and a mouse fibroblast cell line, NIH 3T3. The plasmid constructs, which contain the complete hepatitis B virus genome directing the expression of the luciferase reporter gene, were analyzed by transient transfection assays. The relative orders of the levels of the transcriptional activities of the four promoters were similar in each of the cell lines. The major surface antigen and X-gene promoters displayed the highest activity levels, the core promoter activity level was less than or similar to the activity levels of these two promoters, and the large surface antigen promoter had the lowest activity level in all of the cell lines examined. The core promoter demonstrated an approximately 2- to 20-fold higher relative level of expression in the differentiated hepatoma cell lines, suggesting that this promoter might be preferentially active in these cells. The relative level of activity of the large surface antigen promoter in the differentiated hepatoma cell lines was approximately 5 to 90 times greater than that observed in the other cell lines, indicating that the activity of this promoter is highly specific for differentiation state and cell type. Deletion analysis of the large surface antigen promoter demonstrated that the sequence element responsible for the differentiation state-specific expression from this promoter is located between nucleotides 2719 and 2733 (-90 and -76). Within this sequence element is a binding site (GTTAATCATTACT) for the liver-specific transcription factor hepatocyte nuclear factor 1 (HNF1). This indicates that the preferential expression from the large surface antigen promoter in the differentiated hepatoma cell lines is probably mediated by HNF1 or an HNF1-related transcription factor.
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PMID:Differentiation-specific transcriptional regulation of the hepatitis B virus large surface antigen gene in human hepatoma cell lines. 215 90

In order to investigate the effect of tumor necrosis factor (recombinant TNF-alpha) on hepatoma, we assessed the antitumor activity of TNF-alpha on hepatoma cell line, PLC/PRF/5 in vitro, and combined effects of interferon-gamma (IFN-gamma), that is thought to increase TNF-receptors. TNF-receptors. TNF-alpha for itself, had no significant effect on DNA synthesis and viability, and the production of HBsAg from PLC/PRF/5. On the other hand, treatment of IFN-gamma- combined with TNF-alpha inhibited DNA synthesis and production of HBsAg. The decrease of viability of PLC/PRF/5 was also found in this combination treatment. According to these findings, antitumor activity of TNF-alpha had no effect on PLC/PRF/5 in itself, but was significantly enhanced when treated with IFN-gamma at the same time.
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PMID:[A basic study of cytotoxic effect of tumor necrosis factor-alpha on the hepatoma cell line, PLC/PRF/5]. 215 10

To investigate the effects of iron supplementation on hepatoma cell growth, cells from a human hepatoma cell line, PLC/PRF/5, were grown in RPMI 1640 supplemented with 0, 10 and 20 micrograms/ml of FeSO4 and harvested weekly. At the end of 6 wk culture, cell mass measured 9.6, 14.7 and 13.2 gm, respectively. Amounts of ferritin from these cell masses were 0 (undetectable), 0.89 and 2.27 micrograms/gm of cells. To study the effects of iron deprivation of hepatoma cells, three human hepatoma cell lines (PLC/PRF/5, Hep G2 and Hep 3B) were incubated in tissue culture medium mixed with graded amounts of an iron-chelating agent, desferoxamine, for 48 to 96 hr at 37 degrees C with 5% CO2. Over 50% cell death in PLC/PRF/5 cells and 30% to 50% cell death in Hep G2 and Hep 3B cells were observed 48 to 72 hr after exposure to desferoxamine. Addition of ferric citrate partially reversed the cytotoxic effect of desferoxamine. On the other hand, viability of control cells, human diploid cell line (WI 38), was not affected by desferoxamine. Even after 96 hr exposure to desferoxamine, cell death was only 2% to 4%. These results suggest that (a) iron enhances tumor cell growth, (b) iron induces increased ferritin synthesis by tumor cells in vitro and (c) iron depletion causes tumor cell death but has little effect on normal human diploid cells. These findings should be considered when designing treatment of patients with hepatoma. Iron oversupply in patients with cancer might enhance tumor growth and adversely affect cancer therapy. Iron chelation with desferoxamine might have a place in the treatment of patients with hepatoma in conjunction with other anticancer agents.
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PMID:Effect of iron and desferoxamine on cell growth and in vitro ferritin synthesis in human hepatoma cell lines. 215 79

An accumulation of sulfated and very complex, highly acidic glycolipids was observed in cultured human hepatocellular carcinoma cells. Among the cells tested, PLC/PRF/5 cells contained a significant amount of very complex sulfated acidic glycolipids, and HepG2 cells were characterized as having a large amount of relatively simple sulfated glycolipids. Several monoclonal antibodies (all IgM) directed to these sulfated and highly acidic glycolipids were established. Among them, 49-D6 and 7-E10 were both directed to SM3 (LacCer-II3-sulfate), a relatively simple sulfated glycolipid, and 34-A4 was directed to SD1a (GgOse4Cer II3,IV3-disulfate) and more complex sulfated glycolipids. The other four antibodies, 26-A10, 34-B9, 79-C8, and 16-E10, reacted with unknown highly acidic glycolipids, which were eluted in 0.9-2.7 M ammonium acetate in DEAE chromatography, indicating that these antigenic glycolipids were far more acidic than the usual glycolipids described until now. Analysis of the glycolipids extracted from the hepatocellular carcinoma tissues and cirrhotic livers of patients and from a normal liver with these monoclonal antibodies revealed that sulfated glycolipids having simple carbohydrate structures such as SM3 accumulated significantly in the cirrhotic liver (2 of 4 cases) as well as hepatocellular carcinoma tissue (15 of 17 cases, 88%), and more complex sulfated glycolipids and highly acidic glycolipids were much more specific to hepatocellular carcinoma tissues (10 of 17 cases, 59%) compared to the cirrhotic liver (0 of 4 cases).
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PMID:Accumulation of highly acidic sulfated glycosphingolipids in human hepatocellular carcinoma defined by a series of monoclonal antibodies. 215 66


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