UMLS:C0019204 - FACTA Search

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Query: UMLS:C0019204 (hepatocellular carcinoma)
71,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reuber H 35 hepatoma cells were synchronized by transfer in a serum free medium. Growth was re-initiated by addition of serum. Under these conditions DNA synthesis exhibited a maximum after 24 hours. Chromatin non-histone proteins prepared from cells at various phases of the cell cycle were incubated with [gamma-32P] ATP and the radioactive pattern of protein bound 32P was analysed by electrophoresis on polyacrylamide gels. No radioactive peak was observed in G0. Several peaks appeared 3 hours after the addition of serum. The radioactivity progressively increased until the cells reached the S phase. When most of the cells were in the S phase the radioactivity strongly decreased. Chromatin protein kinase activities were found to increase in late G1 and continued to increase in the S phase. The increase was 65% when phosvitin was the substrate, 100% with casein and histone H1. It is suggested that chromatin phosphorylated proteins could be involved in the mechanism which initiates DNA synthesis in G1 phase cells.
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PMID:Variations in some molecular events during the early phases of the Reuber H 35 cell cycle. II.-Chromatin protein phosphorylation and protein kinases. 51 30

Adenovirus infection of hepatoma cells inhibited transcription of the phosphoenolpyruvate carboxykinase (GTP) (EC 4.1.1.32) (PEPCK) gene and virtually eliminated transcription of a chimeric gene which contained the PEPCK promoter linked to the structural gene for chloramphenicol acetyltransferase (CAT). This effect is due to the viral protein E1A, since adenovirus containing a deletion in the E1A gene did not repress transcription from the PEPCK promoter. Both the 243R and 283R products of the E1A gene were effective. The conserved region 1 (CR-1) domain of E1A was required for this effect. Treatment of hepatoma cells with 8-bromo-cAMP or transfection with plasmids coding for the catalytic subunit of protein kinase A, CAAT/enhancer binding protein alpha (C/EBP), or Jun, all potent inducers of PEPCK gene transcription, did not relieve the inhibition caused by E1A. This inhibition does not appear to be mediated by major enhancer elements and in the PEPCK gene since transcription from the PEPCK promoter containing block mutations in binding domains for C/EBP and cAMP regulatory element binding protein (CREB) was also inhibited by E1A. Transcription of chimeric genes containing two copies each of the major cAMP response domains (CRE-1 and P-3) linked to a neutral promoter and fused to the CAT structural gene was stimulated by the catalytic subunit of protein kinase A, but this effect was totally inhibited by E1A. The strong repressive effect of E1A on PEPCK gene transcription seems to involve an interruption of an obligatory interaction between factors which bind to the cAMP response element in the PEPCK promoter and the TATA box.
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PMID:Adenovirus E1A represses the cyclic AMP-induced transcription of the gene for phosphoenolpyruvate carboxykinase (GTP) in hepatoma cells. 131 Mar 18

Transcriptional activation of the murine Cyp1a-1 (cytochrome P(1)450) gene by inducers such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) (dioxin) requires the aromatic hydrocarbon (Ah) receptor and the interaction of an inducer-receptor complex with one or more of the Ah-responsive elements (AhREs) located about 1 kb upstream from the transcriptional initiation site. We find that treatment of mouse hepatoma Hepa-1 cells with 2-aminopurine, an inhibitor of protein kinase activity, inhibits CYP1A1 mRNA induction by TCDD as well as the concomitant increase in CYP1A1 enzyme activity. Formation of DNA-protein complexes between the Ah receptor and its AhRE target is also inhibited by 2-aminopurine, as determined by gel mobility shift assays. Phosphorylation is required for the formation of Ah receptor-specific complexes, since in vitro dephosphorylation of nuclear extracts from TCDD-treated Hepa-1 cells abolishes the capacity of the Ah receptor to form specific complexes with its cognate AhRE sequences. To determine whether any one of several known protein kinases was involved in the transcriptional regulation of the Cyp1a-1 gene, we treated Hepa-1 cells with nine other protein kinase inhibitors prior to induction with TCDD; nuclear extracts from these cells were analyzed for their capacity to form specific DNA-protein complexes. Only extracts from cells treated with staurosporine, a protein kinase C inhibitor, were unable to form these complexes. In addition, staurosporine completely inhibited CYP1A1 mRNA induction by TCDD. Depletion of protein kinase C by prolonged treatment with phorbol ester led to the complete suppression of CYP1A1 mRNA induction by TCDD. We conclude that (i) phosphorylation is necessary for the formation of a transcriptional complex and for transcriptional activation of the Cyp1a-1 gene; (ii) the phosphorylation site(s) exists on at least one of the proteins constituting the transcriptional complex, possibly the Ah receptor itself; and (iii) the enzyme responsible for the phosphorylation is likely to be protein kinase C.
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PMID:Dioxin-dependent activation of murine Cyp1a-1 gene transcription requires protein kinase C-dependent phosphorylation. 131 72

The hepatocyte nuclear factor 3 (HNF-3) gene family is composed of three proteins (alpha, beta, and gamma) that are transcription factors involved in the coordinate expression of several liver genes. All three proteins share strong homology in their DNA binding domains (region I) and are able to recognize the same DNA sequence. They also possess two similar stretches of amino acids at the carboxyl terminus (regions II and III) and a fourth segment of homology at the amino terminus (region IV). Furthermore, the HNF-3 proteins demonstrate homology with the Drosophila homeotic gene fork head in regions I, II, and III, suggesting that HNF-3 may be its mammalian homolog. In order to define HNF-3 beta protein domains involved in transcriptional activation, we have used a reporter gene, whose transcription is dependent on HNF-3 binding, for hepatoma cell cotransfection assays with expression vectors that produced different truncated HNF-3 beta proteins. A position-independent activation domain which contained conserved regions II and III was identified at the carboxyl terminus of the HNF-3 beta protein (amino acids 361 to 458). Moreover, site-directed mutations that altered the sequences within regions II and III demonstrated their importance to transactivation. The region II-III domain does not possess amino acid sequences in common with other transcription factors and may define a novel activation motif. HNF-3 beta amino-terminal sequences defined by conserved region IV also contributed to transactivation, but region IV activity required the participation of the region II-III domain. Region IV is abundant in serine amino acids and contains two putative casein kinase I phosphorylation sites, a feature similar to protein motifs described for the transcription factors Pit-1/GHF-1 and HNF-1.
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PMID:Hepatocyte nuclear factor 3 beta contains two transcriptional activation domains, one of which is novel and conserved with the Drosophila fork head protein. 132 4

The subcellular distribution and regulation of MAP kinase isoforms in chicken hepatoma DU249 cells was investigated with antibodies directed against peptides patterned after sequences in the mitogen-activated protein (MAP) kinases, sea star p44mpk, and rat p44erk1. MonoQ chromatography of cytosol from these cells afforded the resolution of at least four peaks of myelin basic protein (MBP) phosphotransferase activity, but only one of these (peak II) was stimulated in extracts from phorbol ester-treated cells. A 40- to 41-kDa (p41) doublet on Western blots detected with three different MAP kinase antibodies was coincident with peak II, and it probably corresponded to the avian homolog of p42mapk/erk2. Immunofluorescent studies with DU249 cells and chicken embryo fibroblasts revealed that most of the cross-reactive protein with at least two different MAP kinase antibodies was distributed in the nucleus. Subcellular fractionation studies confirmed a predominantly nuclear localization for p41 MAP kinase. Nocodazole arrest of DU249 cells was exploited for the detection of an M-phase-activated MBP kinase that was resolved from p41 MAP kinase by phenyl-Superose chromatography. Western blotting analysis with antibodies for the cdc2-encoded protein kinase and p13suc1-agarose binding studies allowed positive identification of this MBP kinase as p34cdc2.
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PMID:Immunological characterization of avian MAP kinases: evidence for nuclear localization. 132 21

Recently, it was shown that lipoprotein lipase (LPL) was produced in neonatal but not in adult rat liver. In an attempt to further define the mechanism involved in liver LPL expression, we identified a neonatal mouse hepatoma cell line, BWTG3, capable of producing LPL. The regulation of LPL expression by various extracellular stimuli was investigated in this cell line. Progesterone caused a rise in LPL production by BWTG3 cells. Other hormones tested, such as insulin, glucagon, adrenalin, testosterone, and thyroid hormone, had no effect on LPL production. The effects of progesterone on LPL production showed slow kinetics reaching a maximum 24 h after addition. Cotransfection of a progesterone receptor expression vector with a 5'-LPL-CAT reporter construct resulted in an induction of CAT activity, suggesting that the increase in LPL accumulation after progesterone was linked to transcriptional induction of the LPL gene. Stimuli causing an elevation of protein kinase A activity in the cells also increased LPL production. Three agents capable of elevating intracellular cAMP levels, i.e., forskolin, dBcAMP, and choleratoxin, caused an elevation of LPL production. The increase in LPL activity caused by forskolin and choleratoxin was paralleled by an elevation of LPL mRNA levels, while dBcAMP only induced a small elevation of LPL mRNA levels. The increase in LPL production was shown to be linked to the stimulation of the PKA signal transduction pathway and was apparently transmitted via the transcription factor CREB. No effect of the stimulation of protein kinase C or calcium/calmodulin-dependent kinase on LPL production was detected.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lipoprotein lipase expression in undifferentiated hepatoma cells is regulated by progesterone and protein kinase A. 132 33

The phosphoenolpyruvate carboxykinase (PEPCK) gene is highly expressed in cultured rat hepatoma cells, but extinguished in hepatoma x fibroblast hybrids. Extinction of PEPCK gene expression in hybrids is a polygenic process that involves several fibroblast loci, only one of which (tissue-specific extinguisher-1, TSE1) has been characterized to date. To identify sequence elements of the PEPCK gene that are involved both in TSE1-mediated extinction and in TSE1-independent processes, we assayed expression of chimeric PEPCK transgenes in transiently and stably transfected hybrid cells. We report that TSE1 responsiveness mapped to the PEPCK CRE (cAMP response element), as shown previously for the tyrosine aminotransferase gene. This was expected from the recent identification of the TSE1 gene product as a regulatory subunit of protein kinase A. However, none of the transgenes we assayed were responsive to TSE1-independent extinction mechanisms, suggesting that these controls require DNA sequences and/or chromatin structures that were not present in the transfected reporters. The implications of these findings are discussed.
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PMID:Multiple elements regulate phosphoenolpyruvate carboxykinase gene expression in hepatoma hybrid cells. 133 26

Transcription of the rat serine dehydratase (SDH) gene is induced by glucagon, mediated by the action of cAMP. To identify the nucleotide sequences in the SDH gene responsible for this regulation, we constructed chimeric genes containing different portions of the 5' flanking region of the rat SDH gene fused to the structural sequence encoding the bacterial reporter enzyme, chloramphenicol acetyltransferase (CAT). The transcriptional activities of the fusion genes introduced into the rat hepatoma cell line 7AD-7 were assayed by measuring CAT activity in the cell lysates. Chlorophenylthio-cyclic AMP (CPT-cAMP), a potent protein kinase A activating agent, stimulated the expression of SDH-CAT fusion genes, and these inductions could be enhanced further by the addition of dexamethasone, although the glucocorticoid alone had no effect on CAT activity. Deletion analysis demonstrated that an 80 bp region located approximately 3.5 kb upstream from the transcription initiation site of the rat SDH gene was responsible for stimulation of transcription by CPT-cAMP, whereas the 120 bp region immediately upstream of the cAMP responsive element (CRE)-containing sequences is essential for the enhancement of CPT-cAMP induction by the glucocorticoid.
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PMID:Identification of regions in the rat serine dehydratase gene responsible for regulation by cyclic AMP alone and in the presence of glucocorticoids. 133 28

We have studied the effect of protein kinase-C activation on the regulation of CRH gene expression in the human hepatoma cell line NPLC/PRF/5 (NPLC), the only cell line known to express the endogenous CRH gene. Incubation of NPLC cells with 100 nM 12-O-tetradecanoyl phorbol 13-acetate (TPA), a phorbol ester that activates protein kinase-C, resulted in a rapid (1-h) and prolonged (72-h) increase in CRH mRNA levels, with the maximum increase of 16-fold observed at 24 h. In addition, TPA treatment increased the size of CRH mRNA by approximately 100 nucleotides. This size increase, which was blocked by protein synthesis inhibitors, occurred within 1 h of TPA addition and lasted at least 8 h, with a return toward the baseline size by 24 h. Structural analysis of CRH mRNA revealed two poly(A) addition sites and, as found in human placenta, multiple transcription start sites. The increase in CRH mRNA size was not due to changes in the sites of either transcription initiation or poly(A) addition, but, rather, to a 3-fold increase in the length of the poly(A) tail itself. The ability of TPA to increase CRH mRNA levels in NPLC cells suggests that the protein kinase-C second messenger pathway may be involved in the physiological regulation of CRH gene expression. Increases in CRH mRNA poly(A) tail length potentially may influence CRH mRNA stability or translatability and, thus, may represent a general mechanism by which the protein kinase-C pathway can influence gene expression.
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PMID:Protein kinase-C activation increases the quantity and poly(A) tail length of corticotropin-releasing hormone messenger RNA in NPLC cells. 135 54

Cyclic AMP treatment of hepatoma cells leads to increased protein binding at the cyclic AMP response element (CRE) of the tyrosine aminotransferase (TAT) gene in vivo, as revealed by genomic footprinting, whereas no increase is observed at the CRE of the phosphoenolpyruvate carboxykinase (PEPCK) gene. Several criteria establish that the 43 kDa CREB protein is interacting with both of these sites. Two classes of CRE with different affinity for CREB are described. One class, including the TATCRE, is characterized by asymmetric and weak binding sites (CGTCA), whereas the second class containing symmetrical TGACGTCA sites shows a much higher binding affinity for CREB. Both classes show an increase in binding after phosphorylation of CREB by protein kinase A (PKA). An in vivo phosphorylation-dependent change in binding of CREB increases the occupancy of weak binding sites used for transactivation, such as the TATCRE, while high affinity sites may have constitutive binding of transcriptionally active and inactive CREB dimers, as demonstrated by in vivo footprinting at the PEPCK CRE. Thus, lower basal level and higher relative stimulation of transcription by cyclic AMP through low affinity CREs should result, allowing finely tuned control of gene activation.
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PMID:Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription. 135 12

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