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)

Transcription from the hepatitis B virus (HBV) nucleocapsid promoter is regulated in a cell-type-specific manner and can be modulated by the HBV enhancer I element. Mutagenesis analysis of the nucleocapsid promoter demonstrated that the two Sp1-binding sites (CpB and CpC) in the minimal promoter were the major determinants of transcriptional activity in the dedifferentiated hepatoma cell line, HepG2.1, and the human cervical carcinoma cell line, HeLa S3. In contrast, binding sites for transcription factors located immediately upstream (CpE) and downstream (CpF) of the two Sp1-binding sites were shown to be important determinants of nucleocapsid promoter activity in the differentiated hepatoma cell lines, Huh7 and HepG2. The role of these elements in the regulation of the nucleocapsid promoter activity correlated with the formation of specific DNA-protein complexes between Huh7 and HepG2 nuclear extracts and the CpE and CpF region sequences. Characterization of the influence of the nucleocapsid promoter mutations in the presence or absence of the enhancer I demonstrated that modification of individual transcription factor binding sites does not prevent enhancer-mediated activation of transcription from the nucleocapsid promoter. These results indicate that differentiated-hepatoma-specific transcription factors plus the Sp1 transcription factor interacting with the nucleocapsid promoter and the enhancer I regulatory region contribute to the level of transcription from this HBV promoter.
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PMID:Differentiation-specific transcriptional regulation of the hepatitis B virus nucleocapsid gene in human hepatoma cell lines. 800 54

Biliary glycoprotein (BGP) isoantigens are derived by alternative splicing from a single gene and are the human homologs of rat C-CAM and the mouse Bgp species. These glycoproteins represent a family of cell-adhesion molecules. The mouse Bgp isoforms also act as receptors for the hepatitis viral capsid-protein. BGP is a member of the carcinoembryonic antigen (CEA) gene family, which belongs to the immunoglobulin supergene family, yet it displays restricted expression patterns and unique functions. Since the loss or reduced expression of BGP is associated with human colorectal carcinomas, the elements in its upstream regulatory region were analyzed. A cluster of transcriptional initiation sites and the minimal promoter, located within 150 bp upstream of the major transcriptional start site, were active in human colon carcinoma and hepatoma cells. Unlike the CEA gene, BGP gene transcription was not modulated by a silencer region; repetitive elements in the BGP upstream region were not involved in activation or repression. Footprinting experiments identified two cis-acting elements and mobility-shift assays demonstrated that these elements bound several transcription factors, among them, USF, HNF-4 and an AP-2-like factor. In cotransfection experiments, both the USF and HNF-4 transcription factors transactivate the BGP gene promoter and compete for the same regulatory element. The Sp1 transcription factor, shown to be involved in CEA gene transcriptional regulation, does not bind to the BGP gene promoter. We, therefore, propose that the relative distributions and interactions of these transcription factors mediate distinct transcriptional regulation of the BGP gene in colon and liver; this regulation could be distorted during the oncogenic process.
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PMID:Transcriptional control of the human biliary glycoprotein gene, a CEA gene family member down-regulated in colorectal carcinomas. 805 23

A lambda phage clone containing a promoter region of the human Ah receptor gene was isolated. This clone spanned 13.8 kb and contained the 1st exon, the sequence of which completely matched the reported Ah receptor cDNA. Using RNase protection assay and primer extension analysis, the transcription initiation sites were determined to be 643 and 615 bp upstream of the translational initiation codon ATG. This promoter did not contain a TATA box, while multiple GC boxes were present close to the determined transcription initiation sites. Comparison of the 5' flank sequence of the human Ah receptor with its murine equivalent showed several well conserved regions, containing binding sites for known transcription factors, such as Sp1. The promoter activity was confirmed by transient transfection of chimeric constructs of the Ah receptor gene and reporter gene luciferase into hepatoma HepG2 cells.
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PMID:Molecular cloning of the human AH receptor gene promoter. 807 12

6-Phosphofructo-2-kinase (EC 2.7.1.105)/fructose-2,6-bis-phosphatase (EC 3.1.3.46) catalyzes the synthesis and degradation of fructose 2,6-bisphosphate, a ubiquitous stimulator of glycolysis. The liver (L-type) and muscle (M-type) mRNAs for this bifunctional enzyme arise from distinct promoters of the same gene. We have now characterized in rat hepatoma FTO2B cells another mRNA, which is transcribed from a third promoter of that gene. This F-type mRNA is present in fetal rat liver and muscle, in rat placenta, and in several established rat cell lines. The F promoter contains no TATA box but contains several binding sites for Sp1 and for members of the ets oncogene family. Transfection of FTO2B cells with constructs containing the intact or mutagenized F promoter showed that its activity depends mainly on one of these sites. This site bound a heteromeric FTO2B cell protein indistinguishable from the ets-related GA binding protein alpha/ankyrin-repeats GA binding protein beta transcription factor.
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PMID:Characterization of a hepatoma mRNA transcribed from a third promoter of a 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase-encoding gene and controlled by ets oncogene-related products. 839 65

Apolipoprotein A-I (apoA-I) is a major protein component of plasma high-density lipoprotein in all species studied, and plays an important role in cholesterol homeostasis. In an earlier study, we cloned and structurally characterized the chicken apoA-I gene. In this study, the 5'-flanking region of the chicken apoA-I gene was sequenced and functionally characterized. Sequence analysis of the 510-nucleotide 5' upstream region revealed the presence of TATA and CCAAT boxes. In addition, we identified binding sites for several transcription factors such as Sp1, AP1, and NFI.2. When the 5' fragment was ligated into a promoterless CAT vector and transfected into a chicken hepatocarcinoma cell line (LMH), the bacterial chloramphenicol acetyl transferase (CAT) gene was expressed, suggesting transcriptional regulation is associated with this region. Transfection studies with other 5' deletion constructs revealed that the sequence spanning the region -82 to +87 contained the major transcriptional activity. DNase I footprinting, gel retardation, and Southwestern blot analyses showed that the fragment interacts with nuclear proteins.
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PMID:Characterization of the chicken apolipoprotein A-I gene 5'-flanking region. 839 17

The hepatitis B virus nucleocapsid minimal promoter contains sequence elements which are similar to the Sp1 transcription factor binding site consensus sequence. The interaction of these regulatory elements with Sp1 was examined by DNase I footprinting with purified Sp1 protein and DNase I footprinting and gel retardation analysis with nuclear extracts from human cell lines and was examined functionally with transient transfection assays in human hepatoma and Drosophila melanogaster Schneider line-2 cells. DNase I footprinting identified two regions of the nucleocapsid promoter, representing three recognition elements, that bound purified Sp1. Gel retardation analysis with Huh7 nuclear extracts demonstrated that each of the three recognition elements bound the same or similar transcription factor(s) as that recognized by the Sp1 consensus sequence recognition element. The function of the nucleocapsid promoter elements was examined by transient transfection assays in D. melanogaster Schneider line-2 cells by using these binding sites cloned into a minimal promoter element. Each of these regulatory regions transactivated transcription from the minimal promoter element in response to exogenously expressed Sp1. In addition, the second Sp1 site was shown to be an essential element of the nucleocapsid promoter in human hepatoma cells. This demonstrates that the hepatitis B virus nucleocapsid promoter contains three functional Sp1 binding sites which may contribute to the level of transcription from this promoter during viral infection.
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PMID:Characterization of functional Sp1 transcription factor binding sites in the hepatitis B virus nucleocapsid promoter. 843 25

Previously, we showed that when a DNA fragment extending from -3067 to -2734 of the human apolipoprotein B (apo-B) gene is inserted immediately upstream of an apo-B promoter segment (-139 to +121), transcription from this promoter is reduced by about 10-fold in cultured colon carcinoma cells (CaCo-2) but not in cultured hepatoma cells (HepG2). We postulated that this reducer operates by a mechanism involving active repression of a transcriptional activator that binds to the segment from -111 to -88 of the apo-B promoter (B. Paulweber and B. Levy-Wilson, J. Biol. Chem. 266:24161-24168 1991). In the current study, the reducer element has been localized to a 24-bp sequence from -2801 to -2778 of the apo-B gene that contains a binding site for the negative regulatory protein ARP-1. Furthermore, we have demonstrated that the transcription factor hepatocyte nuclear factor 3 alpha (HNF-3 alpha) binds to the sequence 5'-TGTTTGCTTTTC-3' from -95 to -106 of the apo-B promoter, to stimulate transcription. Transcriptional activation by HNF-3 is repressed when the reducer sequence is inserted immediately upstream of the HNF-3 binding site, suggesting a mechanism by which the reducer-bound protein blocks the activation promoted by HNF-3. Data from cotransfection experiments in which ARP-1 is overexpressed in the absence of its binding site suggest that ARP-1 interacts either directly or via a mediator protein with proteins recognizing the HNF-3 site and that this interaction is sufficient to repress transcriptional activation by HNF-3. Because transcriptional activation by Sp1 is not affected by the reducer, it is unlikely that the reducer interacts directly with basic components of the transcriptional machinery.
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PMID:The mechanism by which the human apolipoprotein B gene reducer operates involves blocking of transcriptional activation by hepatocyte nuclear factor 3. 844 95

We have isolated genomic clones containing the complete exon 1 and the promoter-regulatory region of the E1 alpha gene (BCKDHA) of human branched-chain alpha-keto acid dehydrogenase complex. The cloning was achieved by amplification of a genomic library in the SRB (P2) host strain that allowed the replication of nonstandard DNA structures. The results of this and previous (Dariush, N., Fisher, C. W., Cox, R. P., and Chuang, D. T. (1991) FEBS Lett. 284, 34-38) studies showed that the human E1 alpha gene contains 9 exons, and spans at least 55 kilobases (kb). Exon 1 is 135 bp in length, and contains multiple transcription initiation sites at bases +1, +18, and +22. The complete human E1 alpha cDNA is, therefore, 1,758 bp in length excluding the poly(A)+ tail, and has 27 nucleotides in the 5'-untranslated region. Sequencing of the 5'-flanking region disclosed the absence of a canonical TATA-box in the vicinity of base -30. Several sets of "CAAT" box-like sequences and Sp1 binding-sites are present. Also present are copies of potential AP-2 binding, fat-specific element 1, fat-specific element 2, glucocorticoid-responsive element, and cAMP-responsive element sequences, as well as multiple sets of direct and inverted repeats. The promoter-regulatory region was characterized using deletion constructs and the luciferase reporter assay. The human hepatoma cells (Hep-G2) and Chinese hamster ovary (CHO) cell lines were used as hosts. The results obtained with Hep-G2 cells indicate that the region for high level transcription is located between bases -320 and -115. Extension of the 5'-end of the insert to beyond base -320 markedly reduces promoter activity. The results strongly suggest the presence of inhibitory elements in the region upstream of base -320. Assays in CHO cells show that the region for high level transcription lies between bases -909 and -115. The variation in the region for high level transcription in Hep-G2 and CHO cells may represent cell-type specific differences in the E1 alpha gene promoter function.
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PMID:Characterization of the promoter-regulatory region and structural organization of E1 alpha gene (BCKDHA) of human branched-chain alpha-keto acid dehydrogenase complex. 846 40

We have cloned a cDNA for a novel GC box-binding protein designated BTEB2 from a human placenta cDNA library using rat BTEB cDNA (Imataka et al. (1992). EMBO J. 11,3663-3671. as a hybridization probe. BTEB2 consists of 219 amino acids and contains three contiguous zinc finger motifs at its C-terminus. The zinc finger domains showed 59% and 64% sequence similarity to those of Sp1 and BTEB, respectively. Adjacent to the N-terminal of the zinc finger motifs, a short sequence rich in basic amino acids is conserved between BTEB2 and Sp1. Furthermore, This basic sequence concurs with the N-terminal half of the consensus sequence for basic domains of the proteins containing both helix-loop-helix and leucine zipper motifs. The other region of BTEB2 is notably rich in proline, serine, threonine, and alanine residues. BTEB2 expressed in Escherichia coli showed DNA-binding activity whose specificity was closely similar to that of Sp1. Cotransfection experiments using Hepa-1 cells (a mouse hepatoma cell line) with a BTEB2 expression plasmid and GC box-containing reporter plasmids revealed that BTEB2 apparently activated the expression of the CAT activity. Moreover, when BTEB2 was fused to GAL4 DNA-binding domain, the chimeric protein could enhance the transcription through promoters containing GAL4-binding sites. Analysis of the BTEB2 mRNA by RNA blot analysis demonstrated that the mRNA was expressed specifically in testis and placenta with different sizes, 20S and 28S, respectively, among various organs examined.
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PMID:cDNA cloning and transcriptional properties of a novel GC box-binding protein, BTEB2. 847 2

Blood coagulation Factor X and its activated form Factor Xa play an essential role in the midphase of the clotting cascade. To delineate the mechanisms governing the liver-specific expression of Factor X, we have previously characterized the complete 2.8 kilobase pairs of the 5'-flanking region of Factor X and demonstrated that the first 209 base pairs is sufficient to confer maximal promoter activity in HepG2 cells, a hepatoma cell line that expresses Factor X. We have also shown that mutations at ACTTTG and CCAAT elements located at -56 to -51 and -120 to -116, respectively, significantly reduce the promoter activity. In this report, we demonstrate that Factor X mRNA is primarily but not exclusively expressed in the liver. Using DNase I footprinting analysis, we determine four protein binding sites within the 209-base pair fragment, designated site 1 (-73) to -44), site 2 (-128 to -94), site 3 (-165 to -132), and site 4(-195 to -169). Using gel mobility shift assays in combination with competition and supershift experiments, we demonstrate that hepatocyte nuclear factor 4 and Sp1 bind at site 1, the site which contains the ACTTTG element. Methylation interference assays reveal that HNF-4 and Sp1 contact adjacent sites with minor overlap. HNF-4 and Sp1 appear to bind site 1 in a mutually exclusive fashion. We also demonstrate that HNF-4 can transactivate the Factor X promoter in HeLa cells; mutation at the adjacent Sp1 site further increases the transactivation. Heteromeric transcription factor NF-Y was identified as the protein that binds the CCAAT box at site 2. We conclude that HNF-4 and NF-Y play crucial roles in modulating the activity of the proximal promoter of Factor X.
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PMID:Liver-enriched transcription factor HNF-4 and ubiquitous factor NF-Y are critical for expression of blood coagulation factor X. 856 96

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