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 beta 2-glycoprotein (beta 2gpI) cDNA was isolated from a liver cDNA library and sequenced. The cDNA encoded a 19-residue hydrophobic signal peptide followed by the mature beta 2gpI of 326 amino acid residues. In liver and in the hepatoma cell line HepG2 there are two mRNA species of about 1.4 and 4.3 kb, respectively, hybridizing specifically with the beta 2gpI cDNA. Upon isoelectric focusing, recombinant beta 2gpI obtained from expression of beta 2gpI cDNA in baby hamster kidney cells showed the same pattern of bands as beta 2gpI isolated from plasma, and at least 5 polypeptides were visible.
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PMID:Molecular cloning and mammalian expression of human beta 2-glycoprotein I cDNA. 165 23

A mutational analysis was used to identify structural domains that are important for exocytic transport and proteolytic cleavage of the mouse mammary tumor virus (MMTV) glycoprotein, which is expressed as a multidomain polyprotein. Rat HTC hepatoma cells were transfected with the MMTV glycoprotein gene driven by the constitutive Rous sarcoma virus promoter, with mutant genes encoding a series of polypeptide truncations or with a defective MMTV provirus containing a premature termination codon in the viral glycoprotein gene. Efficient proteolytic maturation and transport of MMTV glycoproteins to the cell surface or extracellular environment required the presence of the transmembrane domain but not the cytoplasmic tail. Two stable truncations retaining the hydrophobic region of the ectodomain in the absence of the transmembrane domain and cytoplasmic tail (trgp67 and trgp58) remained in endoglycosidase H sensitive and uncleaved forms. One of these truncations, trgp58, appeared to be tightly associated with intracellular membranes and strongly bound by heavy chain binding protein, whereas the other truncation, trgp67, was a soluble component of the lumen and persists intracellularly by a heavy chain binding protein-independent pathway. The truncated MMTV glycoprotein additionally lacking the hydrophobic region of the ectodomain was efficiently secreted. Taken together, our results demonstrate that the hydrophobic transmembrane domain of the MMTV glycoprotein is required for proper transport and proteolytic processing, whereas, in the absence of the transmembrane domain, the presence of a hydrophobic region of the ectodomain correlated with retention at an early step in the exocytic pathway.
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PMID:Expression of mouse mammary tumor virus glycoprotein truncations defines roles for the transmembrane domain and ectodomain hydrophobic region in constitutive exocytic trafficking and proteolytic processing. 165 86

Expression of the glycoprotein MII2 antigen originally identified in Zajdela ascites hepatoma cells was investigated in several normal rat tissues and in more or less differentiated tumours using biochemical and immunological approaches. SDS-polyacrylamide gel electrophoresis followed by fluorography or immunoblotting with an antiserum raised against the purified MII2 antigen revealed that this antigen was absent from normal liver cells. ELISA assays, indirect immunofluorescence and immunoprecipitation experiments using the same antiserum showed that this glycoprotein was not expressed in various normal tissues such as liver, spleen, lung, pancreas, intestine and stomach, but it was unexpectedly detected in kidney and thymic tissues. However, the molecular weight of the antigens immunoprecipitated from kidney and thymus was lower than the one of MII2 (Mr of 60,000 versus 110,000-160,000 for purified MII2). No staining was observed in embryonic rat liver at 10 and 20 days of development. Moreover, this antigen was present on the surface of Morris hepatoma 7777, another rapidly proliferating and poorly differentiated hepatocellular carcinoma. In contrast, this antigen was not detected on the surface of in vitro Zajdela hepatoma cells (ZHC) or of partially differentiated hepatomas (Faza) which have recovered some hepatic functions. In addition, the MII2 antigen was found on the human non-hepatic HT-29 tumour cell line, under its undifferentiated form (HT-29 G+ subline). The possible relationships between the expression of this antigen and both the malignant transformation process and the differentiation process are discussed.
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PMID:Immunological screening of a glycoprotein antigen expressed by Zajdela ascites hepatoma cells on normal rat tissues and tumour cells. 165 18

SP-40,40 is a serum glycoprotein consisting of two different subunits (alpha and beta) assembled into a dimer by disulfide bonds. Northern blot hybridization, using total RNA from several cell lines, showed that SP-40,40 is expressed in glioblastoma and testicular tumor cells, as well as hepatoma cells. Spot blot hybridization of flow-sorted human chromosomes, using a SP-40,40 cDNA fragment as a probe, localized the gene for SP-40,40 to human chromosome 8. This gene has been given the designation CLI, for complement lysis inhibitor, by the Human Gene Nomenclature Committee.
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PMID:Assignment of a human serum glycoprotein SP-40,40 gene (CLI) to chromosome 8. 166 Mar 93

1. Five perchloric acid-soluble fractions (PASFs) obtained from ascitic fluids of three patients with primary hepatocellular carcinoma (HCC), a patient with liver metastatic carcinoma (LUC) from ureteral carcinoma and human normal serum (NS) were subjected to DEAE-cellulose column chromatography to separate seven glycoprotein fractions, respectively. 2. In this chromatography, two HCC-PASFs gave a Thomsen-Friedenreich (T)-active glycoprotein, respectively. 3. Other HCC-PASF gave a T-active glycoprotein, two blood group N antigen precursor glycoproteins and an N antigen precursor glycoprotein with T activity. 4. LUC-PASF gave two T-active glycoproteins and an N antigen precursor glycoprotein with T activity. 5. NS-PASF did not give these serologically active glycoproteins.
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PMID:Thomsen-Friedenreich (T)-active glycoproteins, blood group N antigen precursor glycoproteins and N antigen precursor glycoproteins with T activity from ascitic fluids of liver cancer patients. 166 65

We have documented previously that glucocorticoid hormones modulate the posttranslational localization of cell surface mouse mammary tumor virus (MMTV) glycoproteins in the viral-infected M1.54 rat HTC hepatoma cell line. To determine whether glucocorticoids affect the trafficking of individually synthesized MMTV glycoproteins, HTC cells were transfected with a constitutively expressed MMTV glycoprotein gene lacking the viral phosphoprotein and polymerase genes. This construct also allows equivalent levels of MMTV glycoproteins to be compared in the presence or absence of glucocorticoids. Indirect immunofluorescence and immunoprecipitation of radiolabeled cells revealed that in transfected cells the transmembrane MMTV glycoproteins are efficiently expressed, transported to the cell surface, and proteolytically cleaved in the presence or in the absence of the synthetic glucocorticoid dexamethasone. Cell surface immunoprecipitation of [35S]methionine-labeled cells showed that the level of plasma membrane gp78 appeared to be stimulated 2-fold after dexamethasone treatment, even though fluorescence-activated cell sorting revealed no discernible change in the total concentration of cell surface MMTV glycoproteins. Analysis of oligosaccharide side chain maturation through a pulse-chase radiolabeling revealed that the rate of rough endoplasmic reticulum-Golgi transport was essentially identical in dexamethasone-treated and untreated transfected cells and was similar to that observed in dexamethasone-treated M1.54 cells. Thus, in contrast to viral-infected hepatoma cells, mostly constitutive cellular machinery mediates the trafficking and maturation of cell surface MMTV glycoproteins expressed outside of the proviral context. Taken together, our results suggest that the glucocorticoid-stimulated synthesis of nonglycosylated viral components may contribute to or be responsible for the regulated trafficking of MMTV glycoproteins observed in viral-infected rat hepatoma cells.
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PMID:Altered effects of glucocorticoids on the trafficking and processing of mouse mammary tumor virus glycoproteins constitutively expressed in rat hepatoma cells in the absence of nonglycosylated viral components. 166 47

The broad-range proteinase inhibitor alpha 1-inhibitor III (alpha 1I3), a member of the complement C3/alpha 2-macroglobulin protein family, is the prototype of a negatively regulated acute phase protein. During an acute inflammatory reaction alpha 1I3 plasma protein and liver mRNA concentrations are decreased three- to fourfold in rats, and in chronic inflammations the protein concentration is reduced between ten- and 20-fold. In search of a cell culture model to study the regulation of the alpha 1I3 gene by mediators of inflammation, five well-established rat hepatoma cell lines were examined. All five lines constitutively expressed the gene, a marker for a highly differentiated hepatic phenotype, although at less than one-tenth the level of its expression in vivo. In the three hepatoma lines FAZA, FTO2B and FAO1, alpha 1I3 mRNA was decreased by treatment with interleukin 6 (IL6) and glucocorticoids. Among these lines untreated FAO1 cells produced the highest constitutive concentrations of alpha 1I3 mRNA and in FAO1 cells alpha 1I3 mRNA concentrations were decreased up to fourfold in a dose-responsive and time-dependent manner after treatment with IL6 alone or with combinations of IL6 and the synthetic glucocorticoid dexamethasone. Thus, IL6 alone was sufficient to negatively regulate alpha 1I3 mRNA levels in hepatoma cells with similar characteristics as occur during an inflammatory response in the liver. A number of other acute phase mRNA species, including alpha 1-acid glycoprotein, T2-kininogen, gamma-fibrinogen and alpha 2-macroglobulin were induced to higher levels by the same hormonal treatments in FAO1 cells. The fourfold reduction of alpha 1I3 mRNA concentrations in FAO1 cells could be reversed by treatment with 1 microM of a water-soluble derivative of forskolin, an activator of the cyclic AMP pathway. Thus, the effect of IL6 on the expression of the alpha 1I3 gene may involve the activation of the cyclic AMP pathway. In contrast, T2 kininogen mRNA levels were not altered by treatment of FAO1 cells with forskolin, suggesting that IL6 may act on this gene through a different mechanism.
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PMID:Interleukin 6 is a negative regulator of the acute phase alpha 1-inhibitor III gene. 169 10

A C/EBP-like transcription factor, AGP/EBP, that binds to three distinct motifs in the 5'-flanking region of alpha 1-acid glycoprotein gene (AGP) has been identified. Here we report the cloning and properties of cDNA corresponding to mouse AGP/EBP. AGP/EBP and C/EBP share 87% amino acid sequence homology in the "leucine zipper" and its associated DNA-binding domains, while their sequences outside these domains and the sizes of their mRNAs are different. Unlike the limited expression of C/EBP in tissues and cells, AGP/EBP appears to be ubiquitously expressed in tissues like lung, spleen, kidney, heart, testis, and liver and cell lines like p388D1, 129P (hepatoma cell line of C3H/HeJ), FO (mouse myeloma), and L929. Antibody against cloned and expressed AGP/EBP which was raised in rabbits could recognize AGP/EBP from nuclear extract of a number of cells and tissues. On the basis of our findings about the structural relationship and the similarity of motif recognition, we propose that a family of C/EBP-like transcription factors exists.
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PMID:Molecular cloning of a transcription factor, AGP/EBP, that belongs to members of the C/EBP family. 170 Oct 20

The pattern of gene expression in fetal hepatocytes transformed in culture with a hepatocarcinogen (FRL cells) is studied with respect to a range of markers which are either developmentally regulated and/or shown to be expressed at high levels in hepatoma cells. The relative abundance of the respective mRNAs is determined and immunocytochemistry is used to detect the respective proteins in cultured cells. When compared with its normal counterpart, FRL cells retain the expression of transferrin, alpha 1-acid glycoprotein, gamma-glutamyltranspeptidase, and tyrosine aminotransferase at near normal levels, while expression of the liver-specific isoenzymes of pyruvate kinase (L form) and aldolase (B form) is reduced. The cell lines are different in that they fail to express albumin, alpha-fetoprotein, thiostatin and alpha 2-macroglobulin, and they express high levels of M2-pyruvate kinase and aldolase A, markers often found in abundance in hepatoma cells. Therefore transformation has resulted in different effects on different genes. Furthermore, it is of interest to find that the cells coexpress both forms of the pyruvate kinase isoenzymes which does not occur in the normal developing hepatocyte. These results indicate that it is possible to use this model to study changes which accompany transformation of fetal rat hepatocytes. The resulting cell lines have a stable phenotype and retain the changes which result from transformation even after extended passaging. This facilitates comparisons between the precursor cell and the tumor cell, both of which can be maintained under controlled conditions which exist in culture.
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PMID:Gene expression in clonally derived cell lines produced by in vitro transformation of rat fetal hepatocytes: isolation of cell lines which retain liver-specific markers. 170 49

Dipeptidyl peptidase IV (DPP IV) is a serine exopeptidase expressed at high levels in rat kidney, liver and lung. We established eight monoclonal antibodies against partially purified DPP IV from rat liver plasma membranes. By means of a competitive dot blot assay with purified DPP IV, these antibodies were shown to recognize four different epitopes of the glycoprotein, designated A - D. The epitopes are located on the extracellular domain of DPP IV, as shown by papain digestion of liver plasma membranes. Treatment of DPP IV with neuraminidase and glycopeptide N-glycosidase F, as well as incubation of hepatocytes with the alpha-mannosidase I inhibitor deoxymannojirimycin, revealed that epitope A may be formed by a mannose-rich sugar chain and epitope D might represent a complex carbohydrate structure in the mature glycoprotein, while the epitopes B and C are formed by the protein moiety. Concanavalin A reduced the binding of monoclonal antibody to epitope A by 78%. Binding to epitope D was blocked by 73% with wheat germ lectin, and by more than 99% with sialic acid; epitopes B and C were unaffected by any of the lectins or sugars tested. The immunological cross-reactivity with DPP IV from Morris hepatoma 7777 was demonstrated with monoclonal antibodies against epitopes A-C. Epitope D was not recognized on hepatoma DPP IV. However, in addition to DPP IV, four hepatoma plasma membrane glycoproteins were precipitated by the monoclonal antibody against the epitope D, indicating that this epitope is not uniquely restricted to DPP IV.
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PMID:Development of monoclonal antibodies against different protein and carbohydrate epitopes of dipeptidyl peptidase IV from rat liver plasma membranes. 170 62


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