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)

We have studied the biosynthesis of long chain polyunsaturated fatty acids (LC-PUFA) from their precursors in cultured cells undergoing physiological modifications, or under the influence of lipid-lowering drugs or ethanol. The formation of arachidonic acid (AA, 20:4 n-6) from the percursor linoleic acid (LA, 18:2 n-6) in the neuroblastoma cells SK-N-BE is enhanced at early stages of differentiation, and declines when differentiation is complete, in concomitance with maximal accumulation of AA in cell lipids. In the monocytic cells THP-1, the biosynthesis of LC-PUFA is also enhanced by treatment with the HMGCoA reductase inhibitor simvastatin (S), an effect which is reverted by mevalonate and other intermediates of cholesterol synthesis. Maximal activation of LC-PUFA synthesis by S occurs at concentrations lower than those required for maximal inhibition of cholesterol synthesis. In the hepatoma cells HepG2, ethanol decreases the biosynthesis of LC-PUFA while potentiating the incorporation of acetate into cholesterol. LC-PUFA synthesis appears thus to be modulated in the course of cell differentiation and complex interactions between LC-PUFA and cholesterol synthesis occur, as judged from data obtained through pharmacological manipulations.
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PMID:Manipulation of the fate of long chain polyunsaturated fatty acids in cultured cells. 925 Jun 4

Differential cDNA displays between hepatocellular carcinoma and adjacent non-malignant tissues have previously detected a PCR product, hIRH (human intercrine reduced in hepatomas), equivalent to SDF1alpha/PBSF whose mRNA was lost from human hepatocellular carcinoma and other malignant and pre-malignant samples and malignant cell lines. There are no reports to date of the mRNA status of the receptor for hIRH/SDF1alpha/PBSF, CXCR4 in malignant tissues. We report here that there is a reduction in the mRNA expression of CXCR4 in hepatocellular carcinoma as estimated by Northern blot and RT-PCR and compared to the adjacent non-malignant tissue. The average (mean SD) tumor/normal ratio for CXCR4 mRNA expression, determined by RT-PCR, was 0.65 0.36 in 10 pairs of hepatocellular carcinomas. There was no consistent loss of CXCR4 mRNA expression in a range of malignant cell lines. The 3'-non-coding region of hIRH, had typical early response gene element sequences. Despite the presence of these 3'-elements there was no induction of hIRH gene expression in human lung carcinoma A549 cells by tumor necrosis factor alpha, interleukin-2, lipopolysaccharide or phorbol myristic acetate, nor in human melanoma cell line SB-2 by uv irradiation, under conditions which induced the homologue CXC intercrine IL-8 expression. Furthermore, there was no induction of hIRH gene expression, but rather a suppression, upon serum or cytokine addition to serum-deprived fibroblast cell lines, to an in vitro mouse bone marrow preparation, and to monocytic cell line THP-1.
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PMID:Reduced expression of the CXCR4 receptor mRNA in hepatocellular carcinoma and lack of inducibility of its ligand alpha-chemokine hIRH/SDF1alpha/PBSF in vitro. 1020 Mar 43

Serum Amyloid A (SAA) is an acute-phase protein secreted mainly by hepatocytes and is largely associated with high-density lipoprotein (HDL) in plasma. It has been suggested that SAA alters HDL binding to the cell surface and that this in turn changes HDL-mediated cholesterol delivery to cells. Incorporation of SAA into HDL at concentrations equivalent to those found physiologically in moderate inflammation mediated a 1.5-fold increase in the binding of HDL to adherent peripheral blood mononuclear cells but had no effect on binding of the lipoprotein to the monocyte cell lines, U937 or THP-1. SAA incorporation also increased binding to an endothelial cell line, EA.hy.926. Hepatoma cells (HuH-7) showed no change in specific binding of the SAA-enriched HDL particle compared to normal HDL. These results suggest that a specific receptor for HDL-bound SAA is found on differentiated human macrophages and an endothelial cell line, which may have functional significance in lipid metabolism or other macrophage responses during inflammation.
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PMID:Acute phase serum amyloid A protein increases high density lipoprotein binding to human peripheral blood mononuclear cells and an endothelial cell line. 1065 60

The authors have previously demonstrated that the tumour necrosis factor (TNF) -308 G/A polymorphism affects the binding of transcription factors. In transient transfection assays in PMA stimulated U937 monocytes and Jurkat T cells, the A-containing TNF2 promoter has a 2-3-fold greater transcriptional activity than the TNF1 promoter in the presence of the TNF 3'UTR. In this study it was found that a difference in TNF1 and TNF2 promoter activities was only observed in U937 and Jurkat cells, and not in Raji (B cell line), HeLa (epithelial carcinoma cell line), HepG2 (hepatoma cell line) or THP-1 (monocyte), suggesting cell-type specific transcription factors or modifications may be involved in the formation of the -308 protein/DNA complex. Physiological stimulators, TNF and interferon gamma (IFN-gamma) did not cause differential promoter activity between TNF1 and TNF2, but LPS did with only the TNF2 promoter/3'UTR construct being significantly responsive to lipopolysaccharide (LPS) in U937 cells. In U937 cells, the -308 polymorphism affected transcription following differentiation by phorbol myristate acetate (PMA), retinoic acid, PMA plus LPS and PMA plus retinoic acid with an increase in nuclear factor binding to both TNF1 and TNF2 in the -323 to -285 region being observed. The greatest difference between TNF2 and TNF1 promoter activities (5-fold) was observed following PMA plus retinoic acid treatment of transfected U937 cells for 48h. During this time, U937 differentiated into cells with a macrophage-like morphology. An understanding of the cell type and stimuli specific requirements for differential expression of the -308 polymorphism may help elucidate the role the TNF -308 polymorphism plays in diseases where elevated TNF levels are thought to be important.
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PMID:Effects of stimulus and cell type on the expression of the -308 tumour necrosis factor promoter polymorphism. 1067 Dec 95

In the studies reported herein, we show that two complementary experimental models: inbred strains of mice (i.e. C57BL/6 and C3H/HeJ), and a differentiated line of rat hepatoma cells (i.e. L35 cells), require the activation of cytokines by monocyte/macrophages to display bile acid negative feedback repression of cholesterol 7alpha-hydroxylase (CYP7A1). Feeding a bile acid-containing atherogenic diet for 3 weeks to C57BL/6 mice led to a 70% reduction in the expression of hepatic CYP7A1 mRNA, whereas no reduction was observed in C3H/HeJ mice. The strain-specific response to repression of CYP7A1 paralleled the activation of hepatic cytokine expression. Studies using cultured THP-1 monocyte/macrophages showed that the hydrophobic bile acid chenodeoxycholate, a well established potent repressor of CYP7A1, induced the expression of mRNAs encoding interleukin 1 (IL-1) and tumor necrosis factor alpha (TNFalpha). In contrast, the hydrophilic bile acid ursodeoxycholate, which does not repress CYP7A1, did not induce cytokine mRNA expression by THP-1 cells. Chenodeoxycholate activation of cytokines by THP-1 cells was blocked by the peroxisome proliferator-activated receptor gamma agonist rosiglitazone. The expression of cytokines (e.g. IL-1 and TNFalpha) by THP-1 cells paralleled with the ability of these cells to produce conditioned medium that when added to rat L35 hepatoma cells, repressed CYP7A1. Moreover, rosiglitazone, which blocks cytokine activation by macrophages, also blocked the repression of CYP7A1 normally exhibited by C57BL/6 mice fed the bile acid-containing atherogenic diet. The combined data indicate that the activation of cytokines may mediate CYP7A1 repression caused by feeding mice an atherogenic diet containing bile acids.
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PMID:Bile acid induction of cytokine expression by macrophages correlates with repression of hepatic cholesterol 7alpha-hydroxylase. 1082 15

Serum amyloid A (SAA), an acute-phase protein and a precursor of fibrous components in reactive amyloid deposits, is synthesized mainly in the liver under the stimulation of inflammation-related cytokines. In addition, the SAA gene is expressed in monocytes/macrophages, which are believed to play a central role in amyloid fibrillogenesis. Consequently, the pathogenic implication of SAA produced from these cells has been of major concern. Because SAA synthesis at the protein level in such cells has never been analyzed quantitatively, in this study an enzyme-linked immunosorbent assay was generated with a detection level sufficiently high to measure SAA concentrations in the culture supernatants of the human monocytic leukaemia cell line THP-1. SAA secretion by THP-1 with interleukin (IL)-1beta required the presence of dexamethasone as proposed previously. We also found that unidentified components in fetal calf serum (FCS) could induce SAA production by THP-1 in the presence of dexamethasone. These findings are in contrast to the results obtained from hepatoma cell line HepG2, in which IL-1beta alone could induce SAA secretion, while dexamethasone-supplemented FCS could not. The method was able to quantify SAA secreted from cultured human peripheral monocytes. The findings suggest that monocytes produce SAA in almost the same manner as THP-1. Thus, THP-1 cells can be utilized to investigate a distinctive manner of SAA production from monocytes.
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PMID:Serum amyloid A secretion from monocytic leukaemia cell line THP-1 and cultured human peripheral monocytes. 1088 78

Although prior studies have investigated cellular infection by dengue virus (DV), many have used highly passaged strains. We have reassessed cellular infection by DV type 2 (DV2) using prototype and low-passage isolates representing genotypes from different geographic areas. We observed marked variation in the susceptibility to infection among cell types by different DV2 strains. HepG2 hepatoma cells were susceptible to infection by all DV2 strains assayed. Although the prototype strain generated higher titers of secreted virus than the low-passage isolates, this difference did not correspond to positive- or negative-strand viral RNA levels and thus may reflect variation in efficiency among DV2 isolates to translate viral proteins or package and/or secrete virus. In contrast, human foreskin fibroblasts were susceptible to the prototype and low-passage Thai isolates but not to five Nicaraguan strains tested, as reflected by the absence of accumulation of negative-strand viral RNA, viral antigen, and infectious virus. A similar pattern was observed with the antibody-dependent pathway of infection. U937 and THP-1 myeloid cells and peripheral blood monocytes were infected in the presence of enhancing antibodies by the prototype strain but not by low-passage Nicaraguan isolates. Again, the barrier appeared to be prior to negative-strand accumulation. Thus, depending on the cell type and viral isolate, blocks that limit the production of infectious virus in vitro may occur at distinct steps in the pathway of cellular infection.
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PMID:Infection of human cells by dengue virus is modulated by different cell types and viral strains. 1093 88

The ATP-binding cassette transporter G1 (ABCG1) was recently identified as a regulator of macrophage cholesterol and phospholipid transport. This transporter together with ABCA1 belongs to a group of sterol-sensitive ABC proteins which are induced by lipid loading or specific oxysterols. We report here the genomic structure of ABCG1 along with the 5' flanking sequence using library screening and BLAST search analysis. The ABCG1 gene spans more than 70 kb and contains 15 exons. The exon size is between 30 and 1081 bp and the introns range in size from 137 bp to more than 45 kb. All exon-intron boundaries display the canonical GT/AG sequences. Using promoter-luciferase reporter assays in the myeloid cell lines THP-1 and RAW246.7 and the hepatoma cell line HepG2 we could demonstrate the functionality of the ABCG1 promoter and the minimal sequence requirements for gene expression. The TATA-less proximal promoter contains multiple Sp1 binding sites and a consensus sequence for sterol regulatory element binding protein.
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PMID:Genomic organization and characterization of the promoter of the human ATP-binding cassette transporter-G1 (ABCG1) gene. 1107 82

Serum- and glucocorticoid-induced kinase (sgk) is transcriptionally regulated by corticosteroids in several cell types. Recent findings suggest that sgk is an important gene in the early action of corticosteroids on epithelial sodium reabsorption. Surprisingly, the human sgk was reported not to be transcriptionally regulated by corticosteroids in a hepatoma cell line, and thus far no glucocorticoid response element has been identified in the human SGK gene. Since humans clearly respond to both aldosterone and glucocorticoids in cells where sgk action seems to be important, in this study we determined sgk mRNA levels following dexamethasone treatment for various duration in five human cell lines. These cell lines included epithelial cells (H441, T84 and HT29) and lymphoid/monocyte (U937 and THP-1) lines. Using quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), we found that sgk mRNA levels are markedly induced by glucocorticoids in all of the five cell lines studied. Time course analyses revealed that sgk mRNA levels are elevated as early as 30 min after addition of the glucocorticoid, and remain elevated for several hours. Northern analysis in H441 cells confirmed that sgk is an early induced gene. The induction of sgk by dexamethasone was unaffected by cycloheximide, indicating that it does not require de novo protein synthesis. These results indicate that the human sgk, just like its counterparts in other species, is a primary glucocorticoid-induced gene.
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PMID:SGK is a primary glucocorticoid-induced gene in the human. 1117 8

Human carboxypeptidase D (CPD) is a 180-kDa type I membrane protein with three tandem active site domains. CPD is a B-type (or kininase I-type) carboxypeptidase that cleaves C-terminal basic residues from proteins and peptides, such as Arg9 from bradykinin. The human carboxypeptidase D (CPD) gene was found to encompass approximately 88.3 kb of genomic sequence, containing 21 exons ranging in size from 65 to 1813 bp, and 21 introns ranging in size from 112 bp to 35.6 kb. Although CPD and CPM belong to the same metallocarboxypeptidase subfamily, their intron/exon structures differ significantly. Multiple transcription start sites were found in the CPD gene within a GC-rich sequence lacking the typical TATA box, but containing three GC boxes. Luciferase reporter assays with various size constructs containing the promoter region upstream of the start sites showed that it was active in three different cell lines, especially in the human hepatoma cell line HepG2 and the human monocytic cell line THP-1, which have high constitutive expression of CPD.
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PMID:Structural characterization of the human carboxypeptidase D gene and its promoter. 1248 4


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