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 cloned the functional gene coding for the L ferritin subunit by successive rounds of screening of a mouse genomic library using different oligonucleotides so as to avoid cloning the multiple pseudogenes of this rather complex multigene family. The L gene consists in 4 exons interrupted by 3 introns and spanning 1.8 kb. Quantitative measurements of H and L ferritin mRNA in various mouse tissues using a ribonuclease protection assay reveals important variations in the L/H ratio, the liver displaying the highest amount of L mRNA. Functional analysis of 1 kb of upstream sequence by transient transfections into the hepatoma cell line HepG2 shows that the mouse L gene transcription relies upon a minimal 130 bp promoter region containing 1 TATA box and 2 CCAAT motifs. Elements with an enhancing activity specific of hepatic tissue are likely to be located outside of this 1 kb fragment.
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PMID:[Cloning, characterization and expression of mouse ferritin L subunit gene]. 764 56

The effects of different steroids on the expression of angiotensin AT1 receptors by the human hepatoma cell line, PLC-PRF-5 was studied. Dexamethasone and aldosterone decreased the specific binding of [3H]angiotensin II to intact PLC-PRF-5 cells by 57 +/- 4% and 54 +/- 2%, respectively, compared to control, untreated cells. EC50 values for dexamethasone, cortisol and aldosterone were 1.8 +/- 0.6, 40 +/- 6, and 310 +/- 20 nM, respectively, suggesting that these effects were mediated via a glucocorticoid receptor. Scatchard analysis revealed that dexamethasone decreased the number of angiotensin AT1 receptors expressed (50 +/- 4% relative to control) with no change in receptor affinity. Treating cells with dexamethasone in the presence of either an angiotensin converting enzyme inhibitor or an angiotensin II receptor antagonist did not prevent the reduction in angiotensin AT1 receptor expression, ruling out a mechanism involving a dexamethasone induced increase in endogenous angiotensin II production. A ribonuclease protection assay established that the steady state level of angiotensin AT1 receptor mRNA in dexamethasone treated cells was reduced to 34.7 +/- 8.4% of untreated cells. The decrease in the number of angiotensin AT1 receptors expressed on the cell surface after treatment with dexamethasone therefore seems likely to reflect the decreased steady state level of the mRNA coding for this receptor.
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PMID:Glucocorticoids regulate the expression of angiotensin AT1 receptors, in the human hepatoma cell line, PLC-PRF-5. 777 81

Secretion of anionic endo- and xenobiotics is essential for the survival of animal and plant cells; however, the underlying molecular mechanisms remain uncertain. To better understand one such model system--i.e., secretion of bile acids by the liver--we utilized a strategy analogous to that employed to identify the multidrug resistance (mdr) genes. We synthesized the methyl ester of glycocholic acid (GCE), which readily enters cells, where it is hydrolyzed to yield glycocholic acid, a naturally occurring bile acid. The rat hepatoma-derived HTC cell line gradually acquired resistance to GCE concentrations 20-fold higher than those which inhibited growth of naive cells, yet intracellular accumulation of radiolabel in resistant cells exposed to [14C]GCE averaged approximately 25% of that in nonresistant cells. As compared with nonresistant cells, resistant cells also exhibited (i) cross-resistance to colchicine, a known mdr substrate, but not to other noxious substances transported by hepatocytes; (ii) increased abundance on Northern blot of mRNA species up to 7-10 kb recognized by a probe for highly conserved nucleotide-binding domain (NBD) sequences of ATP-binding cassette (ABC) proteins; (iii) increased abundance, as measured by RNase protection assay, of mRNA fragments homologous to a NBD cRNA probe; and (iv) dramatic overexpression, as measured by Western blotting and immunofluorescence, of a group of 150- to 200-kDa plasma membrane proteins recognized by a monoclonal antibody against a region flanking the highly conserved NBD of mdr/P-glycoproteins. Finally, Xenopus laevis oocytes injected with mRNA from resistant cells and incubated with [14C]GCE secreted radiolabel more rapidly than did control oocytes. Enhanced secretion of glycocholic acid in this cell line is associated with overexpression of ABC/mdr-related proteins, some of which are apparently novel and are likely to include a bile acid transport protein.
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PMID:Enhanced secretion of glycocholic acid in a specially adapted cell line is associated with overexpression of apparently novel ATP-binding cassette proteins. 777 23

The human MDR3 (or MDR2) P-glycoprotein is probably involved in the transport of phospholipids from liver hepatocytes into bile (Smit et al. (1993) Cell 75, 451-462). In accordance with this function, MDR3 is highly expressed in human liver, but lower mRNA levels were also found in adrenal, heart, muscle and cells of the B-cell compartment. We have cloned and analyzed the MDR3 promoter region. It is GC-rich, and contains neither a TATA nor a CAAT box, but it does contain multiple putative SP1 binding sites, features also found in so-called housekeeping genes. RNase protection and primer extension analyses indicate that the MDR3 gene has multiple transcription start sites in a GC-rich region with considerable homology to the putative mouse mdr2 promoter. A 3 kb genomic fragment containing the MDR3 start sites directs transcription of a chloramphenicol acetyltransferase (CAT) reporter gene upon transient transfection in the human hepatoma cell line HepG2. This transcription is orientation dependent, and stimulated by a SV40 enhancer, indicating that the 3 kb insert contains the core promoter elements of the MDR3 gene. The promoter region contains several consensus sequences where known or putative liver-specific (C/EBP, HNF5) or lymphoid specific (Pu.1, ets-1) transcription factors may bind.
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PMID:Characterization of the promoter region of the human MDR3 P-glycoprotein gene. 789 60

A segment of 712 bases coding for part of the human stearoyl-CoA desaturase gene was made by polymerase chain reaction (PCR) using primers based on published rat cDNA sequences. The human PCR product was confirmed by DNA sequencing. It was next cloned into a vector from which anti-sense, highly radioactive RNA transcripts were made in vitro using T7 polymerase. The transcripts were used to probe desaturase mRNA in a number of human tumour and control tissues, using a very sensitive solution hybridization/RNase protection assay. Increased desaturase mRNA levels were found in colonic and oesophageal carcinomas and in hepatocellular adenoma; however, no consistent trend was seen in hepatocellular carcinoma. It is suggested that certain classes of tumour may exhibit increased levels of desaturase mRNA.
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PMID:Partial characterization of a cDNA for human stearoyl-CoA desaturase and changes in its mRNA expression in some normal and malignant tissues. 790 40

Ferritin synthesis is regulated at the translational level by iron, but it is likely that transcriptional regulation of H and L genes is responsible for tissue-specific distribution of H and L mRNAs. In order to define the regions important for transcriptional regulation of the mouse ferritin H gene, we have linked the promoter, including the transcription start site, and 5 kilobases of upstream sequence to a reporter gene (human growth hormone). This construct and a series of 5' deletion mutants have been used to transfect erythroid (K562, mouse erythroleukemia (MEL)) and hepatoma (HepG2) cell lines. Measurement of growth hormone in the culture medium and analysis of ferritin-growth hormone transcripts by a ribonuclease protection assay revealed that a 140-base pair minimal promoter is sufficient to confer a high level of expression to the reporter gene in both cell types. In addition, a 180-base pair fragment, lying 4.5 kilobases upstream of the ferritin transcription start site, functions like an inducible enhancer during N,N'-hexamethylene-bis-acetamide-induced differentiation of MEL cells. A perfect match to a consensus binding motif to the erythroid transcription factor NF-E2 is present in this regulatory element, but the mutant NF-E2 enhancer retains the inducible activity in stably transfected MEL cells, and the results from gel retardation assays suggest that protein-DNA complexes that form in vitro between the ferritin enhancer and MEL nuclear extracts do not contain NF-E2. Thus, nuclear factors that mediate inducibility of the ferritin enhancer remain to be identified.
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PMID:Mouse ferritin H subunit gene. Functional analysis of the promoter and identification of an upstream regulatory element active in erythroid cells. 805 Nov 21

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

Considerable evidence has accumulated indicating that overexpression of P-glycoproteins encoded by the multidrug-resistance (mdr) genes is responsible for the development of collateral resistance to a number of structurally and functionally dissimilar cytotoxic compounds in animal cells. There are three mdr genes (mdr1, mdr2, and mdr3) in the mouse genome and two (MDR1 and MDR2) in the human genome; however, only two mouse genes (mdr1 and mdr3) and one human gene (MDR1) can confer multidrug resistance upon transfection into otherwise drug-sensitive cells. Using RNase protection assay we report here that the steady-state levels of mdr1 and mdr3 messenger RNA were elevated in mouse hepatoma cells treated with dexamethasone (Dex); whereas no induction of mdr2 gene was found. Western blot analyses using anti-mdr1 and anti-mdr3 antibodies revealed that the encoded proteins appeared to be increased, but at much reduced levels. The induction was time and Dex concentration dependent. Nuclear run-on experiments demonstrated that the induction was at least in part by transcriptional control. The induction apparently required new protein synthesis since no increases in mdr1 and mdr3 transcripts was found when cultured cells were simultaneously treated with Dex and cycloheximide. Neither mdr1 nor mdr3 gene was induced in the Dex-treated nonhepatoma cell lines, LMtk- and NIH3T3. Similarly, MDR1 messenger RNA levels were elevated in the Dex-treated human hepatoma line, HepG2, but not in the nonhepatoma, HeLa. This study demonstrated that the hormonal regulation of mdr gene expression is gene and cell type specific.
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PMID:Modulation of multidrug resistance gene expression by dexamethasone in cultured hepatoma cells. 810 93

We report the functional and structural analysis of the 5' untranslated region (5'UTR) of human hepatoma HepG2 gamma-glutamyltransferase (GGT) mRNA. Transient expression of a hybrid GGT-luciferase gene in HepG2, MIA-Pa-Ca-2 and MG 63 cell lines shows that this 5'UTR acts as a tissue-specific translational enhancer. Evidence for transcripts with multiple 5'UTR coding for HepG2 GGT was obtained by RNase protection. Computer analysis of this 5'UTR detected the existence of a stable stem and loop structure containing multiple steroid modulatory elements.
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PMID:The 5' untranslated region of the human gamma-glutamyl transferase mRNA contains a tissue-specific active translational enhancer. 810 26

The goal of this work was to study the effect of the most common Egyptian food items, Vicia faba beans (VF) and bran, on the carcinogenicity of dibutylnitrosamine (DBN) precursors (dibutylamine and nitrite). Mice receiving DBN precursors showed a delayed gain in body weight as well as decreased protein level and 5-nucleotidase activity. Acid ribonuclease, alkaline phosphatase, and DNA level and rate of synthesis were significantly increased compared with corresponding controls. Hepatomas and bladder papillomas developed in 60% and 40% of mice, respectively, after nine months of treatment. On the other hand, administration of VF or bran, in addition to DBN precursors, lessened the damage caused by DBN precursors alone, except DNA level and rate of synthesis were elevated. Alkaline phosphatase was also elevated when bran was administered with DBN precursors. However, these elevations were still less than corresponding elevations in mice receiving DBN precursors alone. The incidence of hepatoma was also reduced to only 20% for both groups. Meanwhile, incidence of bladder papillomas was only 20% in mice receiving VF in addition to DBN precursors, and bladder papillomas were completely absent in mice receiving bran in addition to DBN precursors. In vitro studies were also performed to clarify the effect of VF or bran on diphenylnitrosamine (DPhNA) and its formation from its precursors (diphenylamine and nitrite). The study revealed that VF and bran have the ability to eliminate nitrite and DPhNA from the reaction media and to reduce the rate of formation of DPhNA from its precursors. This reaction depends on the concentration and form of VF or bran and the duration of the reaction. Thus it is concluded that some naturally occurring food items, such as VF and bran, could protect humans against the hazardous effect of nitrosamines and their precursors.
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PMID:Effect of Vicia faba and bran feeding on nitrosamine carcinogenesis and formation. 818 23


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