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)

Beta-actin, cyclophilin and glyceraldehyde-3-phosphate dehydrogenase (GAPDH) are all constantly expressed proteins that regulate cellular structures and endogenous cytoarchitectural functions. In this study, we used an in vivo N1S1 rat hepatoma model to examine changes in the expression levels of these housekeeping genes in normal and tumor liver samples. The beta-actin, cyclophilin and GAPDH genes were all up-regulated in tumor groups as compared to the controls. Our results suggest that up-regulation of beta-actin, cyclophilin and GAPDH genes may be essential for oncogenesis in hepatoma.
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PMID:Up-regulation of beta-actin, cyclophilin and GAPDH in N1S1 rat hepatoma. 946 81

The present study was designed to determine whether changes in DNA methyltransferase (DNA MTase) expression are involved in hepatocarcinogenesis. We examined DNA MTase expression in normal liver tissue (with no remarkable histological findings), liver tissue showing chronic hepatitis or cirrhosis, which are generally thought to be precancerous conditions, and hepatocellular carcinomas (HCCs) using the reverse-transcriptase polymerase chain reaction assay. DNA MTase mRNA levels were significantly higher in liver tissue showing chronic hepatitis and cirrhosis (DNA MTase mRNA/beta-actin mRNA ratio = 0.30 +/- 0.22, n = 24, P < 0.01) than in normal liver tissue either from patients with liver metastatic lesions of colonic cancer (0.14 +/- 0.05, n = 6) or from patients with HCCs (0.16 +/- 0.07, n = 3). DNA MTase mRNA levels were even higher in HCC tissue (0.34 +/- 0.18, n = 29). These results suggest that increased DNA MTase expression may be an early event during hepatocarcinogenesis. DNA MTase is a potential target for HCC preventive therapy.
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PMID:Increased DNA methyltransferase expression is associated with an early stage of human hepatocarcinogenesis. 947 34

Vascular endothelial growth factor (VEGF) is an important mediator of vascular development in tumors. We aimed at clarifying the relationship between VEGF mRNA expression and invasion or metastasis of hepatocellular carcinoma (HCC). Reverse transcript-polymerase chain reaction (RT-PCR) was carried out on surgical specimens of 48 patients with HCC. The relative levels of VEGF mRNA expression were measured by determining a ratio between PCR products of VEGF and the endogenous internal standard gene beta-actin. Expression of VEGF mRNA in tumor was found in 76.5% (39/51) of patients, whereas it was 21.69% (11/51) in non tumorous liver. The levels of VEGF mRNA expression in tumors with tumorous emboli and in poor-encapsulated tumors were higher than that without tumorous emboli and in well-encapsulated tumors respectively (p < 0.05 t test). There was no significance in the expression of VEGF mRNA between large HCC (diameter > 5cm) and small HCC (diameter < or = 5cm) (p > 0.05). VEGF may play an important role in the invasion and metastasis of HCC. Angiogenesis in tumor correlates with progression of HCC.
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PMID:Significance of vascular endothelial growth factor mRNA expression in invasion and metastasis of hepatocellular carcinoma. 964 28

5-Amino-4-imidazolecarboxamide riboside (AICAR) is known to stimulate rat liver 5'-AMP-activated protein kinase (AMPK). AMPK is the mammalian homologue of Snf1p in yeast, involved in derepression of glucose-repressed genes. We used AICAR to test if AMPK could also play a role in the regulation of glucose-dependent genes in mammalian cells. At a concentration which induces phosphorylation-dependent inactivation of HMG-CoA reductase, AICAR blocked glucose activation of three glucose responsive genes, namely L-type pyruvate kinase (L-PK), Spot 14 and fatty acid synthase genes in primary cultured hepatocytes, but was without any action on glucose phosphorylation to glucose 6-phosphate and on expression of PEPCK, albumin and beta-actin genes. AICAR was also found to inhibit activation of the L-PK gene promoter by glucose in transiently transfected hepatoma cells. Therefore our results suggest that AMPK is probably involved in the glucose signal pathway regulating gene expression in the liver.
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PMID:The 5'-AMP-activated protein kinase inhibits the transcriptional stimulation by glucose in liver cells, acting through the glucose response complex. 970 98

Cellular adhesion regulatory molecule (CMAR) enhances the adhesiveness of cells to collagen and laminin and is considered to be a candidate anti-oncogene. The purpose of the present study was to investigate the relationship between the expression of CMAR and clinical features of hepatocellular carcinoma (HCC). Small amounts of liver tissue were obtained from HCC and non-cancerous portions of the liver in 29 patients and from normal liver in seven patients with metastatic liver tumour by biopsy under ultrasound guidance. RNA was extracted with acid guanidinium thiocyanate-phenol-chloroform. Expression of CMAR was assessed by quantitative PCR using beta-actin as an internal standard. A 4 b.p. insertion polymorphism at nucleotide 241 of the CMAR coding region was then investigated using extracted RNA to assess the relationship between the expression of variant mRNA of CMAR and HCC carcinogenesis. The relative expression of CMAR was significantly reduced in HCC compared with non-cancerous and normal livers and had a relationship with certain clinical background factors. The reduced expression of CMAR was thought to be closely associated with the progression of HCC. However, the 4 b.p. insertion polymorphism pattern of CMAR was the same between HCC and non-cancerous liver in all cases in which it was found. These results suggest that progression of HCC may be predicted based on the relative expression of CMAR.
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PMID:Expression of cellular adhesion regulatory molecule in hepatocellular carcinoma. 979 84

In hepatocellular carcinoma (HCC), autoantibodies to intracellular antigens are detected in 30-40% of patients. Patients with chronic hepatitis or liver cirrhosis develop HCC, and when this occurs, some patients exhibit autoantibodies of new specificities. It has been suggested that these novel autoantibody responses may be immune system reactions to proteins involved in transformation-associated cellular events. One HCC serum shown to contain antibodies to unidentified cellular antigens was used to immunoscreen a cDNA expression library, and a full length cDNA clone was isolated with an open reading frame encoding 556 amino acids with a predicted molecular mass of 62 kD. The 62-kD protein contained two types of RNA-binding motifs, the consensus sequence RNA-binding domain (CS-RBD) and four hnRNP K homology (KH) domains. This protein, provisionally called p62, has close identity (66-70%) to three other proteins at the amino acid sequence level, and all four proteins may belong to a family having CS-RBD in the NH2-terminal region and four KH domains in the mid-to-COOH- terminal region. The homologous proteins are: KH domain-containing protein overexpressed in cancer (Koc); zipcode binding protein, a protein which binds to a conserved nucleotide element in chicken beta-actin mRNA (ZBP1); and a protein which binds to a promoter cis element in Xenopus laevis TFIIIA gene (B3). p62 protein is cytoplasmic in location, and autoantibodies were found in 21% of a cohort of HCC patients. Patients with chronic hepatitis and liver cirrhosis, conditions which are frequent precursors to HCC, were negative for these autoantibodies, suggesting that the immune response might be related to cellular events leading to transformation. However, the possible involvement of p62 autoantigen as a factor in the transformation process remains to be elucidated.
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PMID:A novel cytoplasmic protein with RNA-binding motifs is an autoantigen in human hepatocellular carcinoma. 1019 Sep 1

The involvement of signaling factors, which are related to serum component, on the regucalcin mRNA expression in the cloned rat hepatoma cells (H4-II-E) was investigated. The change in regucalcin mRNA levels was analyzed by Northern blotting using rat liver regucalcin complementary DNA (0.9 kb of open reading frame). H4-II-E cells were cultured for 2 or 6 h in a medium containing various reagents in the presence of serum (10% fetal bovine serum) after the subconfluent with 3-day-culture. The regucalcin mRNA expression was significantly increased by serum addition. This increase was clearly inhibited by the presence of EGTA (10(-3) M), A23187 (10(-6) M), trifluoperazine (10(-5) M), staurosporine (10(-7) M), or genistein (10(-5) M) with 6-h-culture, although the beta-actin mRNA expression was not altered by the reagents. Meanwhile, the regucalcin mRNA expression was significantly stimulated by the addition of Bay K 8644 (2.5 x 10(-6) M) in the presence of serum. This effect was also seen in the presence of genistein (10(-5) M). The present study suggests that the regucalcin mRNA expression is mediated through signaling pathways which are partly involved in Ca2+-dependent protein kinases and tyrosine kinase in H4-II-E hepatoma cells.
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PMID:Involvement of intracellular signaling factors in the serum-enhanced Ca2+-binding protein regucalcin mRNA expression in the cloned rat hepatoma cells (H4-II-E). 1038 Dec 64

Insulin regulates the rate of expression of many hepatic genes, including PEPCK, glucose-6-phosphatase (G6Pase), and glucose-6-phosphate dehydrogenase (G6PDHase). The expression of these genes is also abnormally regulated in type 2 diabetes. We demonstrate here that treatment of hepatoma cells with 5-aminoimidazole-4-carboxamide riboside (AICAR), an agent that activates AMP-activated protein kinase (AMPK), mimics the ability of insulin to repress PEPCK gene transcription. It also partially represses G6Pase gene transcription and yet has no effect on the expression of G6PDHase or the constitutively expressed genes cyclophilin or beta-actin. Several lines of evidence suggest that the insulin-mimetic effects of AICAR are mediated by activation of AMPK. Also, insulin does not activate AMPK in H4IIE cells, suggesting that this protein kinase does not link the insulin receptor to the PEPCK and G6Pase gene promoters. Instead, AMPK and insulin may lie on distinct pathways that converge at a point upstream of these 2 gene promoters. Investigation of the pathway by which AMPK acts may therefore give insight into the mechanism of action of insulin. Our results also suggest that activation of AMPK would inhibit hepatic gluconeogenesis in an insulin-independent manner and thus help to reverse the hyperglycemia associated with type 2 diabetes.
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PMID:5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase. 1086 40

A cDNA microarray technique, which allows simultaneous analysis of differential expression of mRNA of over 4000 known human genes, was utilized to study the gene expression in 10 pairs of HCC and nontumorous tissues from ethnic Chinese patients in Hong Kong. A total of 211 genes were found to be highly expressed and 147 genes were downregulated in more than 1 out of 10 of the HCC pairs. The results were significant by two-tailed Wilcoxon test (P < or = 0.05 with 95% confidence) on the intensity of each DNA spot of the 10 HCC pairs. Six genes were highly expressed and 10 genes were downregulated in more than 30% of HCC pairs. Results are consistent with other published reports using traditional differential display, subtractive hybridization, or immunohistochemical staining methods. We also detected that beta-actin and glyceraldehyde 3-phosphate dehydrogenase (G3PDH), which have been commonly used as an internal standard control in mRNA expression studies, were highly expressed in HCC when compared with nontumorous tissue. It is concluded that cDNA microarray analysis is an effective method in the detection of differential gene expression in HCC.
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PMID:Differential gene expression of hepatocellular carcinoma using cDNA microarray analysis. 1113 25

A non-radioactive in situ hybridization (ISH) protocol for localization of mRNAs encoding peroxisomal proteins in hepatoma cell lines from humans (HepG2) and rats (MH1C1) is presented. In comparison to a similar procedure reported for tissue sections, the cell culture preparations require only brief fixation in 4% paraformaldehyde and their permeabilization is achieved by a very low concentration (1 microg/ml) of proteinase K. The exclusive localization of transcripts in the cytoplasm of hepatoma cells with the absence of nuclear staining and the completely negative sense controls confirm the specificity of the method. The marked differences in signal intensity between the results of albumin and beta-actin mRNAs which are of high abundance in contrast to moderate to low abundance of peroxisomal mRNAs show the high sensitivity and the wide range of applicability of our protocol. This is also confirmed by divergent results of treatment of hepatoma cell lines with clofibrate and cetaben on mRNA levels of catalase and acyl-CoA oxidase. The ISH results of drug treatment of cell lines are confirmed also by slot blot analysis of total RNA extracts using 32P-labeled probes. Thus the protocol presented here provides a sensitive tool for ISH localization of mRNAs encoding peroxisomal proteins. In combination with immunocytochemistry it may be useful to monitor intercellular differences in expression levels of specific mRNAs in correlation with the abundance of structurally divergent forms of peroxisomes (tubular versus spherical) and their importance in the biogenesis of peroxisomes.
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PMID:Localization of mRNAs encoding peroxisomal proteins in cell culture by non-radioactive in situ hybridization. Comparison of rat and human hepatoma cells and their responses to two divergent hypolipidemic drugs. 1145 50


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