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)

The Retinol-Binding Protein (RBP) is expressed primarily in the liver. The regulatory elements involved in its tissue-specific expression have been identified and mapped to the 5' flanking region of the RBP gene. In this paper heterokaryons and somatic cell-hybrids have been produced and analysed in order to demonstrate that the RBP gene is subject to extinction and to identify the target sequences of this phenomenon. We show here that the gene is extinguished in fusions of hepatoma with a variety of cells of different species and embryonic lineages. The repression is not due to loss of the gene and occurs also when chromosome 10, where the gene is located, is inherited from the expressing parental cell-type. Hybrid clones were transfected with constructs carrying DNA segments of different lengths from the 5' flanking region of the RBP gene fused to a reporter gene. We demonstrate that extinction takes place also on an exogenous RBP-CAT gene, mimicking the phenomenon observed with the endogenous gene in its chromosomal location. Moreover, we identify and map the target sequences of the putative extinguishing function. Our data thus show that extinction of RBP is mediated through the DNA segment that is involved in its tissue-specific expression.
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PMID:Extinction of retinol-binding protein gene expression in somatic cell-hybrids: identification of the target sequences. 225 20

The estrogen response element (ERE) directly linked to a TATA box induces CAT activity in a hormone-dependent manner in Fe 33 cells, the rat hepatoma cell line FTO-2B, stably transfected with the human estrogen receptor (ER). The same promoter construct mediates the stimulation of in vitro transcription. This stimulation is dependent on the presence of the ERE. Induction of transcription in a variety of nuclear extracts derived from mammalian cells is of the same magnitude irrespective of the presence of ER. Similarly, transcription in vitro mediated by B1 vitellogenin 5' flanking sequences in different nuclear extracts is not due to the interaction of the ER with the ERE. Competition analyses with a variety of oligonucleotides reveal that proteins different from the ER, which recognize ERE-like DNA elements, functionally interact with the ERE in vitro. These experiments suggest that ubiquitous proteins related or even identical to the transcription factor USF (MLTF) activate in vitro transcription in an ERE-dependent manner.
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PMID:Transcription factors different from the estrogen receptor stimulate in vitro transcription from promoters containing estrogen response elements. 232 26

Through a series of promoter deletions and gene transfer experiments we have examined the basal regulation and glucocorticoid-mediated repression of the rat epoxide hydrolase gene. Three regions of the 5' flanking sequence were found to influence the basal level of promoter function in H4IIE hepatoma cells. Region A (-891 to -355 bp) contains an apparent repressor of epoxide hydrolase expression, while regions B (-271 to -171 bp) and C (-141 to -85) were found to contain important sequences required for optimal promoter activity. Previous work has demonstrated that dexamethasone represses epoxide hydrolase transcription by approximately 50% in isolated rat liver nuclei, and, in this study, we have demonstrated that the ability of the epoxide hydrolase promoter to drive CAT expression is similarly repressed in H4IIE cells treated with 1 microM dexamethasone. Furthermore, the level of endogenous epoxide hydrolase mRNA is decreased by 70-88% in nontransfected H4IIE cells treated with dexamethasone. Interestingly, promoter activity was not decreased by dexamethasone in COS cells, which lack glucocorticoid receptors. The current data show that sequences from -42 to +110 bp are sufficient to support the dexamethasone response, and, furthermore, they suggest that repression may not require direct interaction of the ligand-receptor complex with the promoter region.
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PMID:Glucocorticoid repression and basal regulation of the epoxide hydrolase promoter. 235 Jan 82

The level of alpha-fetoprotein (AFP) mRNA in HuH-7 human hepatoma cells is elevated by the addition of dexamethasone to the culture medium. To locate the DNA region involved in hormonal regulation of the AFP gene, we constructed recombinant plasmids in which various lengths of the 5'-flanking sequence of the human AFP gene were fused to the CAT gene. Various cell lines were transfected with the recombinant plasmids, incubated with or without 3 x 10(-6) M dexamethasone, and then assayed for chloramphenicol acetyltransferase expression. In hepatoma cells that produce AFP, the dexamethasone treatment resulted in the stimulated chloramphenicol acetyltransferase expression when the transfected plasmids contained 169 base pairs (bp) or longer AFP 5'-flanking sequence. No dexamethasone effect was observed when the 5'-flanking sequence was less than 98 bp long. The dexamethasone stimulation was effectively suppressed by the glucocorticoid antagonist RU486, indicating that this effect is mediated by glucocorticoid receptors. The 71-bp region between positions -169 and -98 contains a nucleotide stretch which is similar to the consensus sequence of the glucocorticoid responsive element (GRE). Partial alterations of this sequence resulted in decreased dexamethasone response. The GRE-containing region stimulated heterologous (SV40) promoter activity in response to dexamethasone treatment in an orientation- and position-independent manner. The GRE and the upstream AFP enhancer function independently from each other.
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PMID:Transcriptional regulation of alpha-fetoprotein expression by dexamethasone in human hepatoma cells. 246 58

pAFP-CAT, a recombinant plasmid containing 5'-flanking sequence from -7 kb to +7 bp of rat alpha-fetoprotein (AFP) gene can drive the expression of the bacterial chloramphenicol acetyltransferase gene in McA-RH7777 and McA-RH8994 rat hepatoma cell lines. Dexamethasone treatment suppresses pAFP-CAT expression in McA-RH7777 cells but increases its expression in McA-RH8994 cells, which mimics the dexamethasone responses of the endogenous AFP gene in both cell lines. However, dexamethasone treatment enhanced pMMTV-CAT expression in both cell lines. These data suggest that the effects of dexamethasone on AFP gene expression may be mediated by different trans-acting factors binding to the specific cis-elements of the 5'-flanking region of the rat AFP gene.
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PMID:The mechanism of the bidirectional regulation of the rat alpha-fetoprotein gene by glucocorticoid hormone. 247 82

Photosensitization induced by tetrabromofluorescein (eosin, 3.8 mumol/L) in ascites hepatoma cells or in normal kidney cells of mice was found to be significant. The cytocidal activity increased in proportion to the concentration of fluorescein as well as with irradiation time. ESR signals were not detected using a trapping agent, 2,2,6,6-tetramethyltetrahydroxy-piperidine (TMHP) which functions as a singlet oxygen probe. No effect on photosensitization by superoxide dismutase (SOD), NaN3, histidine, mannitol or beta-carotene were observed. However, catalase did decrease photosensitization. These results indicate that cytocidal activity is not related to 1O2, O2-. or OH., but is related to H2O2. The cytocidal activity of tetrabromofluorescein in ascites hepatoma cells is stronger than that in normal kidney cells.
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PMID:[Mechanism of active oxygen in cytocidal activity of tetrabromofluorescein]. 248 20

The cytotoxic properties of quinone drugs such as menadione and adriamycin are thought to be mediated through one-electron reduction to semiquinone free radicals. Redox cycling of the semiquinones results in the generation of reactive oxygen species and in oxidative damage. In this study the toxicity of mitozantrone, a novel quinone anticancer drug, was compared with that of menadione in human Hep G2 hepatoma cells. Mitozantrone toxicity in these cells was not mediated by the one-electron reduction pathway. In support of this, inhibition of the enzymes glutathione reductase and catalase, responsible for protecting the cells from oxidative damage, did not affect the response of the Hep G2 cells to mitozantrone, whereas it exacerbated menadione toxicity. In addition, the toxicity of menadione was preceded by depletion of reduced glutathione which was probably due to oxidation of the glutathione. Mitozantrone did not cause glutathione depletion prior to cell death. DT-diaphorase activity and intracellular glutathione were found to protect the cells from the toxicity of both quinones. Inhibition of epoxide hydrolase potentiated mitozantrone toxicity but did not affect that of menadione. Our experiments indicate that mitozantrone toxicity may involve activation to an epoxide intermediate. Both quinone drugs inhibited cytochrome P-450-dependent mixed-function oxidase activity, although menadione was more potent in this respect.
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PMID:The toxicity of menadione and mitozantrone in human liver-derived Hep G2 hepatoma cells. 253 22

By transfections of hepatitis B virus (HBV) DNA into five human hepatoma cell lines with the characteristics of differentiated human hepatocytes, three human hepatoma cell lines possessing partial hepatocyte-associated markers, and one non-liver cell line, we demonstrated that the expression of hepatitis B surface and core genes preferentially occurred in hepatoma cell lines with differentiated hepatocyte-associated characteristics. With a heterologous CAT gene as a reporter, the transcriptional activity of the promoter region containing both the distal (SPI) and the proximal (SPII) promoters of hepatitis B surface gene was found to show a preference for differentiated hepatoma cell lines. The SPI promoter which produces a RNA transcript for the synthesis of the large surface protein shows a strong preference, at least 750-fold, for differentiated hepatoma cells, while the SPII promoter which produces RNA transcripts for the synthesis of the middle and major surface proteins shows a moderate preference, about 20- to 59-fold. Further study indicates that this 750-fold preference of the SPI transcriptional activity for differentiated hepatoma cell lines can be attributed to the regulatory sequences of both the SPI and the HBV enhancer regions. These results also imply the important role of the large surface protein of HBV on the hepatocyte-specific infectivity of this virus.
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PMID:The surface gene promoter of the human hepatitis B virus displays a preference for differentiated hepatocytes. 254 37

The genomic region upstream from exon F (exon IV) of the human aldolase A gene has been studied for its ability to direct the transcription of a reporter gene in vivo. Transfection experiments in human hepatoma cells (Hep 3B) followed by CAT assay, and S1 mapping analysis, demonstrated that: (i) this region is able to drive CAT gene transcription; (ii) all the transcriptional control elements of this promoter are downstream from nucleotide -384 of the longer ubiquitous RNA start site and the sequences between -384 and -262 play a crucial role in transcriptional efficiency; (iii) initiation starting points for two mRNAs exist 61 bp apart. Gel retardation and footprinting assays demonstrated the presence of DNA-protein complexes mainly in the region between -384 and -262 and such ubiquitous binding factors as Sp1 and AP-1.
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PMID:In vivo activity of the most proximal promoter of the human aldolase A gene and analysis of transcriptional control elements. 255 95

Human C-reactive protein (CRP) is the major acute phase reactant during acute inflammation. The human CRP promoter is expressed in an inducible and cell-specific manner when linked to the bacterial CAT gene and transfected into human hepatoma cell cultures. In this paper we analyze the effect of several recombinant cytokines or CRP promoter inducibility in human Hep3B cells. When cytokines are tested singly the major inducer of CRP-CAT fusions is interleukin-6 (IL-6). Maximal CAT gene expression, however, is only achieved when both interleukin-1 beta (IL-1 beta) and IL-6 are present. The response to the two cytokines is cooperative. Cooperativity is maintained when the CRP promoter is linked to a different coding region, that of the bacterial neomycin phosphotransferase II gene. With a series of 5' and 3' deletions we show the existence of two distinct and independent regions responsive to IL-6 and located upstream to the TATA box. The IL-1 effect is exerted at the level of downstream sequences that are probably important for optimal mRNA translatability or nuclear-cytoplasmic transport. Inducibility is not influenced by the activation of protein kinases C or A and does not require new protein synthesis.
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PMID:Dual control of C-reactive protein gene expression by interleukin-1 and interleukin-6. 255 73


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