UMLS:C0019204 - FACTA Search

Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Target Concepts:

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

Vitronectin in a cell-adhesion molecule whose expression is temporally and spatially regulated in vivo, but whose regulatory mechanism of transcription is unknown. In this study, we characterized the mouse vitronectin gene promoter. Luciferase expression vectors cloned the successive 5'- or 3'-deletions of the 5'-flanking region upstream of the luciferase gene and were transfected into the human hepatoma cell line HepG2. The assay of luciferase activity in the transfected cells revealed that a 38 base pair (bp)-element (positions +3 to +40) displays promoter activity. A consensus sequence consisting of a TATA box and initiator is shown around the transcription initiation site of the mouse vetronectin gene, but the GC box is not shown. Site-directed or deleted mutagenesis against a consensus sequence of TATA box and initiator could not abolish the promoter activity. These results induce that the putative TATA box and initiator are not involved in the promoter activity, and that the vitronectin promoter lacks the TATA box, initiator and GC box. To characterize trans-acting factors involved in promoter activity, a DNA fragment (position -74 to +95) was subjected to gel shift assay using nuclear proteins extracted from HepG2 cells. One shifted band was detected by the gel shift assay, suggesting that a nuclear protein binds to the promoter region. Results of the DNase I foot printing assay and gel shift assay demonstrate that the nuclear proteins can bind to the 38 bp-element, which has promoter activity. The nuclear protein is a putative trans-acting factor involved in transcription initiation.
...
PMID:TATA-less mouse vitronectin gene promoter: characterization of the transcriptional regulatory elements and a nuclear protein binding site on the promoter. 963 27

We previously reported that the transcription of the human macrophage stimulating protein (MSP) gene was positively regulated by the binding of NF-Y to the CAATT sequence in the promoter region of this gene. Here we confirmed our previous results and further characterized the MSP promoter. Luciferase assay with deletion constructs showed the importance of the region, +32 to +39, for the promoter activity in Hep3B cells. Two nuclear protein-DNA probe (+15 to +40) complexes, C1 and C2, were detected by electrophoretic mobility shift assay. C2 was specific to hepatoma cells and contained hepatocyte nuclear factor-4 (HNF-4). DNase I footprinting with recombinant HNF-4 located another HNF-4-binding site in the distal region, -89 to -54. Mutations in the CAATT or the proximal HNF-4-binding site significantly reduced the promoter activity in Hep3B cells and HNF-4-transfected HeLa cells, whereas mutations in the distal HNF-4-binding site had no effect. The close proximity between the CAATT and the proximal HNF-4-binding site suggested that a direct contact between NF-Y and HNF-4 might be important. Protein-protein interaction between the A-subunit of NF-Y and HNF-4 was detected by a yeast two-hybrid system. The binding of in vitro translated HNF-4 to immobilized NF-YA and in vitro translated NF-YA to immobilized HNF-4 was also detected. These results suggest the binding of HNF-4 to the proximal HNF-4-binding site directs the basal transcription of the MSP gene, and the maximal promoter activity may depend on the direct association between HNF-4 and NF-Y.
...
PMID:Positive regulation of the human macrophage stimulating protein gene transcription. Identification of a new hepatocyte nuclear factor-4 (HNF-4) binding element and evidence that indicates direct association between NF-Y and HNF-4. 966 24

The rat branched-chain-2-oxo-acid dehydrogenase (BCOD) kinase mRNA is transcribed from a TATA-less promoter that has GC-rich sequences and two putative Sp1 binding sites near the transcription start site. We demonstrated previously that the 5' region of the kinase gene, base pairs -128 to +264, contained promoter activity when assayed using luciferase as a reporter (Huang and Chuang (1996) Biochem. J. 313, 603-609). To define DNA elements required for efficient expression of the kinase gene, nested deletion constructs of the above promoter region fused with a luciferase reporter gene were transfected into cultured H4IIE (hepatoma) and NRK-52E (kidney) cells. The results showed that the region between nucleotides -58 and +21 was indispensable for the kinase basal promoter activity. Methylation-interference and mutagenesis-promoter assays identified nucleotides -50 to -40 (ACAACTCCCA) as cis-acting DNA sequences that are required for nuclear protein binding and efficient promoter activity. Gel-supershift analysis with anti-Sp1 antibody suggested that the nuclear protein capable of binding to the -58 oligonucleotide (bp -58 to -34) was immunologically related to the Sp1 protein. The -58 oligonucleotide formed a DNA-protein complex with recombinant Sp1 protein with an affinity approximately ten-fold lower than that of the consensus Sp1 oligonucleotide. Co-transfection of the Sp1 expression plasmid and the -58 promoter construct into Drosophila Schneider cells revealed that Sp1 contributed to the kinase basal promoter activity by binding to the non-consensus site in the -58 region. Deletion of two consensus Sp1 binding sites (bases -150 to -140 and bases +29 to +38) in the kinase gene did not affect the basal promoter activity. Therefore binding of Sp1 or Sp1-like proteins to the above single non-consensus Sp1 sequence in the -58 region plays a major role of transactivating basal expression of the BCOD kinase.
...
PMID:Mechanism for basal expression of rat mitochondrial branched-chain-2-oxo-acid dehydrogenase kinase [corrected]. 972 81

The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at a chromosomal translocation break point in acute promyelocytic leukaemia. To elucidate if PML may be involved in hepatocellular carcinoma (HCC), the expression of PML was analysed using immunohistochemistry in human HCC and hepatitis tissues. Our studies demonstrated overexpression of PML protein in the PML-oncogenic domain (POD) structure in 50% of HCC (11/22). Enhanced expression and cytoplasmic localisation of PML was associated with cirrhosis. Increased expression of PML was also found in liver abscesses. However, in colon metastasis to the liver, the expression of PML was moderate to low, although strong expression was seen in the surrounding interstitial cells, macrophages and lymphocytes, an indication of the inflammation process associated with tumour growth. Most interestingly, strong expression of PML was found in neoplastic cells at the periphery of the tumours, but progressively decreased in cells at the centre of the tumours, which may be associated with an altered transform phenotype or apoptosis. The altered expression of PML indicates that this nuclear protein may play an important role in cellular response to stress and inflammation, as well as in compensatory cell growth.
...
PMID:Altered expression of the growth and transformation suppressor PML gene in human hepatocellular carcinomas and in hepatitis tissues. 984 49

Apolipoprotein (apo) C-I is a constituent of triglyceride-rich lipoproteins (TGRL) that interferes with their hepatic clearance. Functional polymorphism in the apoC-I gene has not been established. We determined that an Hpa I site variably present at -317 relative to the apoC-I gene is produced by a 4-bp CGTT insertion. The apoC-I Hpa I alleles showed an ethnically distinct pattern of linkage disequilibrium with the alleles of the adjacent apoE gene. The frequency of apoC-I Hpa I-positive (H2) with apoE varepsilon2 was 0. 98, without significant ethnic difference. In contrast, the frequency of H2 with apoE epsilon4 was 0.85 in European-Americans but only 0.55 in African-Americans (P < 0.001). The frequency of H2 with apoE epsilon3 was 0.02 in European-Americans and 0.08 in African-Americans (P < 0.001). African-American apoE epsilon3/epsilon3 carriers of apoC-I H2 had 19% lower fasting triglyceride levels than H1 homozygotes (P = 0.03) along with 18% higher HDL-cholesterol levels (P = 0.02). ApoB levels were 21% lower (P = 0.002). H2-allelic reporter-gene constructions showed 50% higher expression in transient transfection studies. We localized the source of this difference in expression to the CGTT insertion itself. Deletion studies of the H1 allele showed a negative transcriptional effect of the polymorphic region. An H1 oligodeoxynucleotide showed specific binding of a hepatoma-cell nuclear protein not evident with an H2 oligodeoxynucleotide. The H2 sequence may decrease the binding of a negatively acting transcription factor, leading to overexpression of apoC-I. This may produce a functional effect on lipoprotein levels but confirmation is needed in other populations.
...
PMID:A common Hpa I RFLP of apolipoprotein C-I increases gene transcription and exhibits an ethnically distinct pattern of linkage disequilibrium with the alleles of apolipoprotein E. 986 49

The tumor suppressor gene p53 is known to be involved in the negative regulation of cell growth. Proliferating cell nuclear antigen (PCNA), which is a nuclear protein and a component of the DNA replication process, is also involved in growth regulation. Both have been studied as progression markers in various tumors including hepatocellular carcinoma. In the present study, the aberrant p53 protein and PCNA expressions in non-tumoral liver diseases were investigated. Using monoclonal antibodies anti-p53 (D07-DAKO) and anti-PCNA (PC10-DAKO), 149 samples were stained, including 10 normal and 10 tumoral control liver tissues. p53 Overexpression was detected in 52 specimens (35%) whereas PCNA positivity was found in 96 (64%). There were 21 different pathological entities but most of the positive samples could be grouped into four types of diseases; namely, non-specific reactive hepatitis, steatohepatitis, chronic hepatitis and cirrhosis. Statistical analyses performed on these groups revealed that p53 positivity was found to be significantly higher in steatohepatitis (P < 0.05), while PCNA positivity did not show any statistical significance. The number of samples showing both p53 and PCNA positivity was 42 but their coexistence was not found to be significant. Certain cytological alterations like nuclear pleomorphism, steatosis and cholestasis, in addition to necroinflammatory activity, were evaluated for their possible impact on p53 and/or PCNA positivity. Necroinflammatory activity in steatohepatitis and steatosis in chronic hepatitis was found to be significant for p53 positivity (P < 0.05). In contrast, nuclear pleomorphism in non-specific reactive hepatitis was found to be significant for PCNA positivity (P < 0.05).
...
PMID:P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases. 1033 76

Smad7 is a regulatory Smad protein that is able to antagonize signal transduction by transforming growth factor-beta (TGF-beta) and activin receptors. To characterize the regulation of Smad7 at the transcriptional level, we isolated the promoter region of the mouse Smad7 gene. When the Smad7 promoter luciferase reporter gene (-408 and +112 bp) was expressed in human hepatoma (HepG2) cells, its transcriptional activity was increased following TGF-beta or activin treatment. In addition, this region of the Smad7 promoter was stimulated by ectopic expression of Smad3 as well as constitutively active TGF-beta and activin receptors, indicating that Smad7 transcription was modulated by the signaling downstream those two receptors. A gel mobility shift assay indicated that a DNA fragment spanning -408 to -126 base pairs (bp) was able to directly bind purified Smad4. Furthermore, a consensus Smad3-Smad4 binding element (SBE) was discovered in this region of the promoter with a palindromic sequence of GTCTAGAC. A 33-bp Smad7 promoter fragment containing this SBE was able to bind Smad3 and Smad4. In human embryonic kidney 293 cells, the expression of constitutively active TGF-beta type I receptor was able to induce the formation of a Smad3- and Smad4-containing nuclear protein complex that bound the SBE. In HepG2 cells, TGF-beta1 treatment could induce the formation of an endogenous SBE-binding complex. Taken together, these data provided the first evidence that Smad7 transcription is regulated by TGF-beta and activin signaling through direct binding of Smad3 and Smad4 to the Smad7 promoter.
...
PMID:Regulation of Smad7 promoter by direct association with Smad3 and Smad4. 1055 22

The transcriptional regulation of the fibronectin (FN) gene in hepatoma cells by phorbol myristate acetate (PMA) was investigated. PMA increased the synthesis and mRNA levels of FN and its promoter activity in Hep3B hepatoma cells. The PMA-induced activation of FN expression was blocked by a protein kinase C (PKC) inhibitor and did not require a new protein synthesis. Deletion analysis revealed that the sequence between positions -69 and +136 of the FN gene was responsible for the PMA induction. Two PMA-inducible nuclear protein complexes were found to bind to a putative NF-kappaB site at -41 and were identified as a p65/p50 heterodimer and a p50/50 homodimer of NF-kappaB family. Mutations in the -41 NF-kappaB site, however, did not block the PMA induction of the FN promoter but rather enhanced it. Overexpression of p65 increased the FN promoter activity. While overexpression of p50 alone did not affect the promoter activity, it decreased the p65-induced activation of the FN promoter. Mutations in the -41 NF-kappaB site attenuated the p50-mediated suppression of the p65 transactivation of the FN promoter. Deletion of the sequence between +1 and +136 decreased the basal and PMA-induced activities of the FN promoter. This study shows that PMA induces the transcription of the FN gene in hepatoma cells via the PKC pathway. The DNA sequence between +1 and +136 is responsible, at least in part, for the PMA-induced activation of the FN gene, while the -41 NF-kappaB binding site plays as a negative regulatory element for it. In addition, this study is the first to show a role for NF-kappaB p65 in the transcriptional activation of the FN gene.
...
PMID:Transcriptional regulation of fibronectin gene by phorbol myristate acetate in hepatoma cells: a negative role for NF-kappaB. 1064 41

The characterization of the binding of nuclear protein on the 5'-flanking region of the rat regucalcin gene was investigated. Nuclear extracts from rat liver and H4-II-E hepatoma cells were used for oligonucleotide competition gel mobility shift assay. An oligonucleotide between position -523 and -506 in the 5'-flanking region of the rat regucalcin gene, which contains a nuclear factor I (NF1) consensus motif TTGGC(N)(6)CC, competed with the probe for the binding of the nuclear proteins from rat liver and H4-II-E cells. The mutation of TTGGC in the consensus sequence caused an inhibition of the binding of nuclear factors. The presence of Bay K 8644, insulin, and phorbol esters could stimulate the binding of the nuclear factors to the TTGGC region of the rat regucalcin gene in H4-II-E cells. The specific mutation introduced in this region, which was ligated to a luciferase reporter gene, reduced significantly the effects of Bay K 8644, insulin, and phorbol esters in stimulating the regucalcin gene transcriptional activity in H4-II-E cells. These results suggest that the specific nuclear factor binds to the NF1-like sequence, which can stimulate the transcriptional activity, in the promoter region of regucalcin gene in liver cells.
...
PMID:Involvement of hepatic nuclear factor I binding motif in transcriptional regulation of Ca(2+)-binding protein regucalcin gene. 1069 12

Gap junctional intercellular communication facilitates liver homeostasis and growth control in the liver. The major gap junction protein expressed by hepatocytes is connexin32 (Cx32) and non-parenchymal hepatic cells do not express this gene. We investigated the regulation of Cx32 transcription by trans-activating factors in liver cells. Transient transfection assays using deletions of the rat Cx32 promoter (nt -753 to -33) linked to the luciferase gene were performed in MH1C1 rat hepatoma cells that express endogenous Cx32 compared with WB-F344 rat liver epithelial cells that do not. The basal promoter element was located within nt -134 to -33 and was 1.4-fold more active in MH1C1 cells than WB-F344 cells whereas the entire promoter fragment (nt -754 to -33) was four-fold more active in MH1C1 cells. Specific nuclear protein-DNA complexes that bound to Sp1 consensus sites within the basal promoter were formed using nuclear extracts from both types of cells. Additional promoter sequences increased promoter activity more strongly in MH1C1 cells than WB-F344 cells and this was correlated with the binding of hepatocyte nuclear factor-1 (HNF-1) to two HNF-1 consensus sites centered at -187 and -736. Expression of HNF-1 and binding to these elements was only observed with MH1C1 cells. Other specific protein-DNA complexes were formed, however, that included YY-1- and NF-1-containing complexes, but these were not related to promoter activity. Dexamethasone increased Cx32 promoter activity and expression in MH1C1 cells, but had little effect in WB-F344 cells and did not alter protein-DNA complex formation. These data suggest that Sp1 is responsible for Cx32 promoter basal activity, that HNF-1 determines the cell-specific expression of Cx32, and that dexamethasone increases Cx32 expression through other mechanisms.
...
PMID:Liver cell-specific transcriptional regulation of connexin32. 1076 May 74

<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>