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

Hepatocyte growth factor (HGF) is a potent mitogen for hepatocytes; however, in certain human hepatoma cell lines, the growth is inhibited by HGF. In the present study, the effect of HGF on the alpha-fetoprotein (AFP) gene expression was analyzed in PLC/PRF/5 human hepatoma cells. HGF did not inhibit cell proliferation, but dose-dependently suppressed AFP secretion at the concentrations of 10 ng/ml or less. By Northern blot analysis, the levels of AFP mRNA were suppressed by HGF, whereas the levels of beta-actin mRNA used as a control did not show any significant changes. In the transient chloramphenicol acetyltransferase plasmid transfection assays, the AFP promoter activity was repressed by HGF, in contrast, the AFP enhancer activity was not affected by HGF. These results suggest that the AFP gene expression is down-regulated by HGF through the suppression of its promoter activity in human hepatoma cells.
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PMID:Hepatocyte growth factor down-regulates the alpha-fetoprotein gene expression in PLC/PRF/5 human hepatoma cells. 128 Apr 22

A variety of gene constructs containing carp beta-actin regulatory sequences were tested for their ability to drive transient expression of the chloramphenicol acetyltransferase reporter gene in 3 fish cell lines: carp epithelial cells (EPC), rainbow trout hepatoma cells (RTH149), and rainbow trout fibroblasts (RTG2). The constructs showed a wide variation in their levels of expression, and there were significant differences in the effects of transcriptional elements in the 3 cell lines. Sequences that enhanced expression in EPC cells were inhibitory in RTH149 and RTG2 cells. All cell lines exhibited the presence of nuclear trans-acting factors that could bind to implicated transcriptional control elements. On the basis of the cell culture results, selected constructs were examined for activity in early carp development. Constructs active in embryos and fry were further tested and found to express transgenes in adult fish.
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PMID:Selection of promoters for gene transfer into fish. 130 23

9-deoxy-delta 9,delta 12-13,14-dihydro-prostaglandin D2 (delta 12-PGJ2) is a potent inhibitor of proliferation of tumor cells. In the present study, the effect of delta 12-PGJ2 on the alpha-fetoprotein(AFP) and the albumin gene expression was analyzed in HuH-7 human hepatoma cells. delta 12-PGJ2 inhibited the cell growth and reduced the medium AFP concentrations dose-dependently. To determine whether this decline of AFP depends only on the relative decrease in cell numbers by delta 12-PGJ2, or is in part, due to the decrease in the cellular AFP synthesis by delta 12-PGJ2, Northern blot analysis was performed in this study. By Northern blotting, it was shown that delta 12-PGJ2 caused a marked reduction in the levels of the AFP mRNA and the albumin mRNA. In contrast, the level of the beta-actin mRNA was not changed by delta 12-PGJ2. In the transient chloramphnicol acetyltransferase plasmid transfection experiments, delta 12-PGJ2 did not suppress the AFP enhancer activity, which possibly regulates both the AFP and the albumin gene expression in HuH-7 hepatoma cells, but resulted in the selective repression of the AFP and the albumin promoter activity. These results suggest that delta 12-PGJ2 suppresses not only cell growth but also expression of the AFP gene and the albumin gene at the transcriptional level in human hepatoma cells.
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PMID:Inhibitory effect of prostaglandin delta 12-PGJ2 on cell proliferation and alpha-fetoprotein expression in HuH-7 human hepatoma cells. 137 88

Transforming growth factor beta 1 (TGF-beta 1) is known to inhibit hepatocyte growth in vitro and in vivo. In this study, we analyzed the effect of TGF-beta 1 on alpha-fetoprotein (AFP) and albumin gene expression in HuH-7 human hepatoma cells. TGF-beta 1 inhibited cell growth in a dose dependent manner. The cellular secretion rate of AFP but not albumin was suppressed significantly by TGF-beta 1. TGF-beta 1 caused a significant reduction in the level of AFP mRNA. In contrast, the levels of albumin mRNA or beta-actin mRNA were not changed by TGF-beta 1. In transient transfection experiments, TGF-beta 1 resulted in selective repression of AFP promoter activity. These results suggest that TGF-beta 1 is one of the key factors involved in the differential regulation of the AFP gene and the albumin gene.
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PMID:Transforming growth factor beta 1 differentially regulates alpha-fetoprotein and albumin in HuH-7 human hepatoma cells. 170 21

Insulin has rapid pleiotropic effects on cellular metabolism. In certain cell types, insulin can cause morphological changes by inducing rearrangements of cytoskeletal components, but the regulation of cytoskeletal gene expression by insulin has not been previously described. In the present work insulin was found to rapidly, but transiently, increase transcription of the cytoskeletal beta-actin and alpha-tubulin genes in rat H4IIE hepatoma cells. Insulin-induced transcription of beta-actin mRNA was evident within 5 min and was maximal by 10-15 min at 1000% above control levels. beta-Actin transcription was induced at insulin concentrations as low as 5 x 10(-12) M insulin and was maximal at 5 x 10(-9) M. Transcription of the alpha-tubulin gene was also rapidly stimulated by physiological concentrations of insulin, but only to 300-400% above basal levels. For both the beta-actin and alpha-tubulin genes, the induction of transcription was transient, with a return to basal levels by 60-120 min. Transcription of neither the skeletal or cardiac alpha-actin gene nor the beta-tubulin gene was altered by insulin administration. Messenger RNA levels for the beta-actin and alpha-tubulin genes increased, but to a lesser extent than transcription, since these mRNAs were abundant and stable before the transient induction of transcription. Inhibitors of protein synthesis, in the presence or absence of insulin, also acutely stimulated transcription of these genes.
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PMID:Induction of cytoskeletal gene expression by insulin. 173 64

Regulation of expression of the genes for the low density lipoprotein receptor (LDLR) and 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) is of central importance in the control of cholesterol metabolism and thus in influencing the concentration of low density lipoprotein in the plasma. This can be studied by investigating the effects of factors (hormones, drugs, etc.) on the levels of mRNA for these genes. An RNase protection assay is reported for measurement of the levels of mRNA for the LDLR and HMGR. Several probes have been developed for these genes, together with probes for the "housekeeping" genes, beta-actin and glyceraldehyde-3-phosphate dehydrogenase. Various conditions in the assay have been examined and optimised, e.g. conditions for solution hybridization and RNase digestion and the use of "sense" RNA standards. The assay allows accurate measurement of approximately 2 x 10(7) copies of LDLR and HMGR mRNAs, which is equivalent to the number of copies present in approximately 1 x 10(6) human dermal fibroblasts and approximately 5 x 10(5) Hep G2 liver hepatoma cells cultured in 10% fetal calf serum. The average number of copies of mRNA per cell was estimated in fibroblasts and Hep G2 cells under various conditions of regulation of the LDLR and revealed the following: [table: see text] Under the chosen conditions 10 copies per cell was the detection limit for the assay. The effect of these treatments on the number of copies of mRNA per cell for beta-actin and glyceraldehyde-3-phosphate dehydrogenase was also determined.
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PMID:A sensitive RNase protection assay for the quantitation of the mRNAs for the LDL receptor and HMG-CoA reductase in human total RNA. Effects of treatments on cells in culture designed to up- and down-regulate expression of the LDL receptor. 182 10

We report that the concentration of phosphoenolpyruvate carboxykinase (PEPCK) mRNA increased 5- to 10-fold when H4IIEC3 rat hepatoma cells were cultured at high compared to low density. The magnitude and direction of this response were mRNA specific, as the mRNAs encoding tyrosine aminotransferase and albumin increased approximately 20%, whereas the mRNAs encoding beta-actin and alpha-tubulin decreased 40% and 20%, respectively. Paracrine or autocrine mechanisms were not responsible for the density effect, since conditioned medium or frequent medium changes had only a modest effect on the abundance of PEPCK mRNA. Culture of H4IIEC3 cells at low density or on collagen promoted a flattened morphology and low PEPCK mRNA levels. At high density, cells assumed a cuboidal shape on both plastic and collagen and expressed high PEPCK mRNA levels. Induction of PEPCK mRNA by high density culture did not involve increased intracellular cAMP, since treatment with 8-(4-chlorophenylthio)-cAMP was synergistic with density. High cell density increased PEPCK run-on transcription approximately 3-fold, while PEPCK mRNA increased more than 6-fold. These observations suggest that high culture density increases PEPCK mRNA by increasing its transcription and possibly stabilizing PEPCK mRNA. The response could be coupled to the regulation of cell shape, as a close relationship between cell shape and gene expression has previously been shown to be important in the development and maintenance of tissues and organs. The PEPCK gene in H4IIEC3 cells could provide a useful model in which to study the poorly understood mechanisms involved in coordinating form and function.
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PMID:Culture at high density increases phosphoenolpyruvate carboxykinase messenger RNA in H4IIEC3 hepatoma cells. 207 26

Using the combination of a subtracted library and differential hybridization, a 409-base pair cDNA was identified that corresponds to a mRNA that is induced 2-3-fold when rat Fao hepatoma cells are subjected to amino acid starvation for 12 h. While this mRNA species was induced during starvation, others such as beta-actin, Cu-Zn superoxide dismutase, glyceraldehyde-3-P, and histone H4 were decreased in abundance to 25-50% of their original levels. The induction of the amino acid starvation-induced (ASI) mRNA was repressed when starved cells were returned to a medium supplemented with amino acids. Tissue distribution analysis showed the ASI mRNA, approximately 650 base pairs in length, to be present in every rat tissue tested. The cDNA clone has been sequenced and appears to correspond to the 3'-most end of the mRNA. The cDNA sequence includes the poly(A) tail, two potential polyadenylation signal sequences, and an open reading frame that we presume to be a portion of the coding sequence. The ASI cDNA will be used to investigate the molecular mechanisms for amino acid-dependent regulation of protein expression by mammalian cells.
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PMID:Molecular cloning of an amino acid-regulated mRNA (amino acid starvation-induced) in rat hepatoma cells. 221 64

The low-density-lipoprotein (LDL)-receptor mRNA content of human hepatoma (Hep G2) cells has been estimated from densitometric scans of autoradiograms obtained following the hybridisation of Northern blots of a poly(A)-rich RNA fraction with a 32P-labelled cDNA probe for the LDL-receptor gene. The recovery of beta-actin mRNA was used to correct for losses occurring during the preparation of the poly(A)-rich RNA. The content of LDL-receptor mRNA was reduced when the cells were pre-incubated in medium containing foetal calf serum, 25-hydroxycholesterol, or LDL, compared to that measured in cells which had been pre-incubated in medium containing lipoprotein-deficient serum (LPDS). When insulin (100 mU/ml) was included in pre-incubation medium containing LPDS, the amount of LDL-receptor mRNA increased approximately twofold. The level of beta-actin mRNA was not significantly increased by insulin treatment. Addition of insulin to incubation medium containing LPDS also overcame the suppressive effect of exogenous LDL on the cellular content of mRNA for the LDL receptor. These findings suggest that one action of insulin in these cells may be to promote transcription of the LDL-receptor gene by a mechanism that can override the sterol regulatory pathway.
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PMID:Regulation of low-density-lipoprotein-receptor mRNA by insulin in human hepatoma Hep G2 cells. 247 39

The feasibility of using HepG2 human hepatoma cells to study the regulation of the expression of the cytochrome P4501A2 gene (CYP1A2) was examined. The reverse transcription-polymerase chain reaction (RT-PCR) assay revealed that HepG2 cells constitutively express CYP1A2 and are able to respond to 3-methylcholanthrene (3MC) by an induction of CYP1A2 mRNA. In these studies, selected sequences from intron-exon junctions were used as mRNA-specific primers for both CYP1A2 and the beta-actin gene. The level of induction was quantitated based on two parameters within the exponential phase of the amplification: the difference in the number of cycles that yields the same level of amplification and the efficiency of the PCR reaction. Using this method, it was estimated that the CYP1A2 steady-state mRNA level increased to a maximum of 12-fold at 24 h after exposure of the cells to 3MC. Both a reduction in basal expression as well as an increased accumulation of CYP1A2 mRNA appeared responsible for the overall induction at 24 and 48 h. These results suggested that the HepG2 cell line would be appropriate for studying the regulation of CYP1A2 expression.
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PMID:3-Methylcholanthrene-mediated induction of cytochrome P4501A2 in human hepatoma HepG2 cells as quantified by the reverse transcription-polymerase chain reaction. 752 47


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