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)

Amino acid deprivation of rat hepatoma cells induced the levels of a 612-base pair mRNA termed ASI (Shay, N. F., Nick, H. S., and Kilberg, M. S. (1990) J. Biol. Chem. 265, 17844-17848). The ASI mRNA was present at levels equal to or greater than actin in every rat tissue tested. The corresponding full-length cDNA was cloned, and the present report demonstrates that the deduced 184-residue amino acid sequence shares greater than 30% identity to a number of bacterial and chloroplast L22 ribosomal proteins, including those from Escherichia coli and Halobacterium halobium. A monospecific anti-peptide antibody was produced that upon immunochemical analysis of subcellular fractions of rat liver recognized a band in the microsomal fraction and, more specifically, reacted with a single polypeptide in the ribosomal large subunit fraction. The antibody did not react with any proteins of the mitochondrial large subunit, but did recognize a protein in human liver homogenate at the same relative mobility (23 kDa) as that observed for rat liver.
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PMID:Identification of an amino acid-regulated mRNA from rat liver as the mammalian equivalent of bacterial ribosomal protein L22. 189 96

We have previously shown that BDS.1 rat hepatoma cells are hypersensitive to the antiproliferative effects of glucocorticoids, and secrete a glucocorticoid suppressible mitogenic activity (denoted GSM). Sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed that GSM purified to near homogeneity migrated as a 28-kDa protein under nonreducing conditions and as a single 15-kDa polypeptide in the presence of sulfhydryl reducing agents suggesting a homodimeric structure. Anti-platelet-derived growth factor (PDGF) A-chain specific antibodies selectively immunodepleted the mitogenic activity which can be extracted from nonreducing gels in the 26-30-kDa fraction and, in Western blots, recognized the 15-kDa reduced form of GSM. Western blot analysis further showed that dexamethasone suppressed the level of secreted PDGF A-chain protein in BDS.1 cells but not in glucocorticoid receptor-deficient hepatoma cells. Northern blots revealed that dexamethasone reduced expression of the PDGF A-chain 2.3- and 1.7-kilobase transcripts in proportion to the level of detectable PDGF-AA protein. Similarly to PDGF-AA, the hepatoma cell-derived GSM has a potent angiogenic activity. Taken together, our results demonstrate that the predominant glucocorticoid suppressible mitogen secreted from rat hepatoma cells is a PDGF A-chain homodimer and suggest that in vivo glucocorticoids may potentially regulate hepatoma growth by modulating PDGF-stimulated tumor vascularization.
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PMID:Identification of the glucocorticoid suppressible mitogen from rat hepatoma cells as an angiogenic platelet-derived growth factor A-chain homodimer. 191 57

The human hepatitis B viral (HBV) genome contains a conserved open reading frame known as the X-gene which is capable of encoding a polypeptide of 16.565 kDa. The corresponding protein has so far not been identified directly in HBV-infected cells, but in transient transfection assays the X-gene encodes a product that functions as a transcriptional transactivator. To characterize the subcellular distribution, stability and post-translational modifications of X-protein in human hepatoma HepG2 cells, we have established a vaccinia virus expression system. As the major X-gene product, a protein with an apparent molecular weight of 16 kDa, and reacting with an X-protein-specific antiserum, was expressed from recombinant vaccinia virus. In indirect immunofluorescence assay, X-protein appeared to be distributed throughout the cells, with a tendency to localize at the nuclear periphery and to accumulate in granules as its levels increased. By subcellular fractionation, we found about one-third of X-protein associated with the fraction defined as the nuclear framework. In pulse-chase experiments, X-protein decayed with a bimodal half-life of 15 min and 3 h. X-protein having a half-life of about 15 min was found associated with the Triton X-100 detergent-soluble fraction of HepG2 cells, while that associated with the insoluble fraction turned over more slowly. By metabolic labeling with [32P] orthophosphate, we show that X-protein is capable of being phosphorylated. Modification by phosphorylation could play an important role in the regulation of X-protein function.
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PMID:Phosphorylation and rapid turnover of hepatitis B virus X-protein expressed in HepG2 cells from a recombinant vaccinia virus. 192 99

A cell line, HuH-33 was cultured in vitro from a patient with hepatocellular carcinoma. This cell line has been in continuous culture over 12 month period with slow growth potential. HuH-33 was composed spindle-or polygonal-shaped cells as a major population. Chromosome number of the cells were widely distributed even in the primary culture. HuH-33 was transplantable into nude mice and secreted alpha-fetoprotein, albumin, beta 2 microglobulin, ferritin and tissue polypeptide antigen.
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PMID:[Tissue culture course of a human hepatoma cell line]. 196 86

The dominant insulin-stimulated ribosomal protein S6 kinase activity was purified to near homogeneity from insulin-treated 32P-labeled rat H4 hepatoma cells and found to copurify with a 70-kDa 32P-labeled polypeptide. The dominant S6 kinase purified from livers of cycloheximide-treated rats is also a 70-kDa polypeptide. Antiserum raised against rat liver S6 kinase specifically immunoprecipitates the purified 32P-labeled H4 hepatoma insulin-stimulated S6 kinase. This antiserum also specifically precipitates insulin-stimulated S6 kinase activity directly from cytosolic extracts of H4 cells. Immune complexes prepared from the cytosol of 32P-labeled H4 cells contain several 32P-labeled polypeptides; only a 70-kDA 32P-labeled peptide, however, is specifically displaced by preadsorption of the antiserum with nonradioactive rat liver S6 kinase. Insulin treatment increases the 32P content of the immunoprecipitated 70-kDa S6 kinase polypeptide 3- to 4-fold over basal levels; 32P-labeled serine, some 32P-labeled threonine, but no 32P-labeled tyrosine are detected after partial acid hydrolysis. Tryptic peptide maps indicate that the insulin-stimulated S6 kinase purified from 32P-labeled H4 cells is phosphorylated at multiple sites distinct from those which participate in autophosphorylation in vitro. Autophosphorylation of rat liver S6 kinase in vitro does not modify S6 kinase activity. The S6 kinases purified from liver of cycloheximide-treated rat and H4 hepatoma insulin-stimulated enzyme are each completely deactivated by incubation with protein phosphatase type 2A in both autophosphorylating and 40S S6 phosphorylating activities. The phosphatase 2A-deactivated 70-kDa S6 kinase is neither reactivated nor phosphorylated by partially purified insulin-stimulated microtubule-associated protein 2 kinase, in experiments where Xenopus S6 kinase II undergoes phosphorylation and partial reactivation. Thus insulin activates the 70-kDa S6 kinase by promoting phosphorylation of specific serine/threonine residues on the enzyme polypeptide, probably through activating an as-yet-unidentified serine/threonine protein kinase distinct from microtubule-associated protein 2 kinase.
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PMID:Insulin activates a 70-kDa S6 kinase through serine/threonine-specific phosphorylation of the enzyme polypeptide. 212 50

In the course of investigating the neoplastic alterations of protein phosphatases, the particulate fractions of rat liver and AH-13, a strain of rat ascites hepatoma, were chromatographed on DEAE-cellulose and assayed for protein phosphatase using glycogen synthase D and phosphorylase a as substrates. The synthase phosphatase activity of rapidly growing AH-13 was due almost entirely to a divalent cation-inhibited protein phosphatase, tentatively designated phosphatase N, the level of which was elevated remarkably in the hepatoma as compared with liver. Other hepatomas including primary hepatoma induced with 3'-methyl-4-dimethylaminoazobenzene also exhibited high levels of this phosphatase. Phosphatase N exhibited Mr = 49,000 (gel filtration) and has been partially purified with little alteration in properties. Partially purified phosphatase N was inhibited by divalent cations, rabbit skeletal muscle polypeptide inhibitor-2 and heparin, and released the catalytic subunit of type-1 protein phosphatase upon tryptic digestion. It is therefore apparent that phosphatase N is a type-1 protein phosphatase. There is some evidence to suggest that the high levels of phosphatase N in neoplastic cells are due primarily to enhanced synthesis of its non-catalytic (regulatory) subunit.
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PMID:Particulate-associated protein phosphatases of rat hepatomas as compared with the enzymes of rat liver. 215 61

Hepatitis B virus (HBV) is the causative agent of hepatocellular carcinoma (HCC) in man. The HBV genome is a circular partially double-stranded DNA molecule of about 3.2 kb. The HBV genome contains four structural genes coding for the HBV envelope (HBsAg) and core (HBcAg/HBeAg) proteins, endogenous DNA-polymerase with the additional enzymatic activity of a reverse transcriptase and polypeptide X functioning as a trans-activator of cellular and viral genes. HBV DNA integration in the genomes of HCCs and hepatocytes of HBV carriers is an important evidence establishing a relationship between the HBV infection and the development of HCC. The mechanism of HBV DNA integration into the cellular genome and the possible role of integrated HBV DNA sequences in the malignant transformation of hepatocytes are discussed.
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PMID:[Human hepatitis B virus and hepatocellular carcinoma]. 215 10

A trimer of hepatitis delta virus (HDV) cDNA in a retrovirus expression vector was transfected into subclone of the PLC/PRF/5 human hepatoma cell line, and a stable cell line (H1 delta 9) was clonally selected that supported the synthesis of both genomic and antigenomic sense HDV RNA. The H1 delta 9 cell line also expressed hepatitis delta antigen (HDAg) in cell nuclei in three distinct morphological patterns, including patterns typically seen in HDV-infected livers. HDAg expression was restricted to the smaller (p24) of the two HDAg-associated polypeptides in early passages of the H1 delta 9 cell line, but continuous passage of the cells resulted in increasing of expression of the larger (p27) HDAg-specific polypeptide. Passage of the H1 delta 9 cells also led to sustained expression of monomeric HDV RNA and a reduction in the levels of dimeric- and trimeric-HDV RNA. This was accompanied by an attenuation of virus-related cytotoxicity which was a feature of early cell passage numbers. HDV RNA replication in these cells was resistant to actinomycin D suggesting that replication was not dependent on continued expression from the transfected HDV cDNA and thus was likely to be self-sustaining.
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PMID:Hepatitis delta virus RNA, protein synthesis and associated cytotoxicity in a stably transfected cell line. 216 31

The aim of our work was to assess the performance of tissue polypeptide antigen in detecting hepatocellular carcinoma in cirrhotic patients, while also checking for any influence of liver dysfunction on the serum level of the marker. One hundred and twenty-five consecutive cirrhotic patients, 35 with and 90 without, hepatocellular carcinoma were studied. Tissue polypeptide antigen had a different distribution in the two groups and the best diagnostic accuracy with 48.6% sensitivity and 85.6% specificity was found at the cut-off value of 240 UL-1. In cirrhotic patients significant linear correlations were found between tissue polypeptide antigen and alanine-transaminase, aspartate-transaminase, G-glutamyl-transpeptidase and alkaline phosphatase; there was no correlation with bilirubin or pseudo-cholinesterase. In patients with hepatocellular carcinoma a significant linear correlation was found only with alanine and aspartate transaminase and G-glutamyl-transpeptidase. The analysis of covariance still showed a significant difference between mean tissue polypeptide antigen levels in the two groups also accounting for covariates. These results suggest that: a) the liver dysfunction may be involved in increasing tissue polypeptide antigen values; b) tissue polypeptide antigen has a different distribution in cirrhotic patients with and without hepatocellular carcinoma also accounting for covariates; these findings further support the specificity of tissue polypeptide antigen.
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PMID:The serum tissue polypeptide antigen in the detection of hepatocellular carcinoma in cirrhotic patients. 217 22

Biosynthetic radiolabeling studies demonstrate that A-431 cells, a human epidermoid carcinoma cell line, and human keratinocytes synthesize and secrete C3 as two disulfide-linked polypeptide chains of 120 and 75 kD. Moreover, epithelial cell-derived C3 co-migrates in SDS-PAGE with that produced by HepG2 cells, a human hepatoma cell line previously used to elucidate complement component biosynthesis. Pulse-chase studies in A-431 cells demonstrate that epithelial cell-derived C3 is produced as a 195-kD precursor molecule, pro-C3, which is processed intracellularly by limited proteolysis into 120- and 75-kD C3 alpha and beta chains. Comparative studies demonstrate that A-431 cell-derived C3 is synthesized, processed, and secreted in parallel but in lower quantity than that produced by HepG2 cells. Treatment of biosynthetically labeled A-431 cell culture supernatants with normal human serum and zymosan produces C3 alpha chain cleavage and specific C3 fragments that are not present in control culture supernatants treated with heat-inactivated human serum and zymosan. Northern blot analysis of total cellular RNA extracted from A-431 cells, human keratinocytes, and HepG2 cells reveals quantitative identity of a 5.1-kb C3 mRNA species in these three cell types. Epithelial cell-derived C3 may play an important role in local inflammatory and immunologic reactions including such reactions in human skin. Moreover, epithelial cell C3 synthesis may have direct relevance to the recent demonstration of C3d,g within selected normal primate epithelial basement membranes, including epidermal basement membrane.
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PMID:A-431 cells and human keratinocytes synthesize and secrete the third component of complement. 225 Jan 3


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