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 isolated HFREP-1, a gene that is overexpressed in a hepatocellular carcinoma from a lambda gt10 cDNA library constructed from the mRNA of the hepatocellular carcinoma specimen using subtractive and differential cDNA cloning. The largest cDNA insert contained 1231 base pairs encoding 312 amino acids. The deduced protein sequence contained a hydrophobic leader peptide and the putative protein sequence showed marked homology with beta- and gamma-subunits of fibrinogen and other fibrinogen-related proteins. However, the HFREP-1 protein lacked a platelet-binding site, a cross-linking region and a thrombin-sensitive site, which are crucial for fibrin clot formation. The expression of the gene was studied in various organs in the rat and in several human carcinoma cell lines, and was found to be specific to liver and hepatocellular carcinoma cell lines. We suggest that the HFREP-1 gene is a new member of the fibrinogen family and that further data on the gene are important for a better understanding of the development of hepatocellular carcinomas.
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PMID:Molecular cloning and initial characterization of a novel fibrinogen-related gene, HFREP-1. 839 Feb 49

We have previously identified several novel genes, which are differentially expressed among human normal liver and hepatocellular carcinomas (HCCs). The full-length liver fibrinogen-related gene-1 (LFIRE-1) cDNA was cloned from the human normal liver cDNA library. LFIRE-1 is highly homologous to HFREP-1 with discrepancy at 5' untranslated region (UTR) and encodes the same fibrinogen-related protein, which suggest that these two sequences might be alternative splicing forms of the same gene, LFIRE-1/HFREP-1, located at human chromosome 8p22. The LFIRE-1 and HFREP-1 are specifically expressed in normal human liver tissue, but reduced or undetectable in most of HCC specimens at both RNA and protein level. Furthermore, the reduction or nonexpression of LFIRE-1/HFREP-1 is significantly associated with the degree of tumor differentiation. Loss of heterozygosity (LOH) analysis revealed allelic loss of LFIRE-1/HFREP-1 on chromosome 8p22 in 57.1% (24/42) of HCC specimens. We detected three inactivation mutations among 45 cases of HCC specimens examined, two of which lost the remaining allele and the third had a replacement of conserved cysteine residue with glycine residue. Notably, the downregulation of LFIRE-1/HFREP-1 expression is frequently associated with allelic loss. The reduction of LFIRE-1/HFREP-1 expression by antisense approach enhances cancer cell proliferation and colony formation in soft agar. Moreover, restoration of exogenous wild-type LFIRE-1/HFREP-1 expression but not LFIRE-1/HFREP-1 missense mutations in human HCC cells inhibited their anchorage-dependent or -independent growth in vitro, and suppressed their tumorigenicity in nude mice. In conclusion, our data demonstrated that liver-specific gene LFIRE-1/HFREP-1 was frequently downregulated and might possess growth suppressor activity in HCC.
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PMID:LFIRE-1/HFREP-1, a liver-specific gene, is frequently downregulated and has growth suppressor activity in hepatocellular carcinoma. 1498 37

Molecular characterizations of hepatocellular carcinoma have indicated frequent allelic losses on chromosomes 4q, 8p, 16q and 17p, where the minimal deleted regions have been further defined on 4q12-q23, 4q31-q35, 8p21-p22, 16q12.1-q23.1 and 17p13. Despite these regions are now well-recognized in early liver carcinogenesis, few underlying candidate genes have been identified. In an effort to define affected genes within common deleted loci of hepatocellular carcinoma, we conducted transcriptional mapping by high-resolution cDNA microarray analysis. In 20 hepatocellular carcinoma cell lines and 20 primary tumors studied, consistent downregulations of novel transcripts were highlighted throughout the entire genome and within sites of frequent losses. The array-derived candidates including fibrinogen gamma peptide (FGG, at 4q31.3), vitamin D binding protein (at 4q13.3), fibrinogen-like 1 (FGL1, at 8p22), metallothionein 1G (MT1G, at 16q12.2) and alpha-2-plasmin inhibitor (SERPINF2, at 17p13) were confirmed by quantitative reverse transcription-polymerase chain reaction, which also indicated a more profound downregulation of FGL1, MT1G and SERPINF2 relative to reported tumor-suppressor genes, such as DLC1 (8p22), E-cadherin (16q22.1) and TP53 (17p13.1). In primary hepatocellular carcinoma examined, a significant repression of MT1G by more than 100-fold was indicated in 63% of tumors compared to the adjacent nonmalignant liver (P = 0.0001). Significant downregulations of FGG, FGL1 and SERPINF2 were also suggested in 30, 23 and 33% of cases, respectively, compared to their nonmalignant counterparts (P < 0.016). In summary, transcriptional mapping by microarray indicated a number of previously undescribed downregulated genes in hepatocellular carcinoma, and highlighted potential candidates within common deleted regions.
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PMID:Positional expression profiling indicates candidate genes in deletion hotspots of hepatocellular carcinoma. 1698 Sep 51

The investigation of novel genes involved in the derangement of glucose and lipid metabolism is of particular importance in understanding the development of metabolic syndrome (MS). In the present study, bioinformatic analyses were carried out to explore the structures and roles of the proteins encoded by the four cDNA sequences identified in our previous studies as associated with MS. Homology analyses demonstrated that the proteins encoded by Sequence 1, Sequence 2, Sequence 3, and Sequence 4 were homologous with fibrinogen gamma polypeptide, liver fibrinogen-like 1, chromosome 10 open reading frame 104, and an unnamed protein product, respectively. Because the structures were well-known for fibrinogen gamma polypeptide and liver fibrinogen-like 1, further analyses were performed only for Sequence 3 and Sequence 4. Analyses of functional domains showed that the predicted proteins encoded by Sequence 3 and Sequence 4 had multiple phosphorylation and myristoylation sites. These results indicated that the two predicted proteins might be intermediate proteins in some signaling pathways. In order to explore the possible association of Sequence 3 with MS, HepG2 cells, a human hepatoma cell line, were treated with different concentrations of glucose (mannitol as osmotic control) for 48 h. Glucose at concentrations of 22 and 33.3 mM significantly increased the mRNA expression of Sequence 3 compared to glucose at 5.6 mM while mannitol had no significant effect on the mRNA expression of Sequence 3. These results indicated that the mRNA expression of Sequence 3 was positively associated with glucose higher than physiological concentrations.
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PMID:Bioinformatic analyses and an expression study of a novel gene associated with metabolic syndrome. 2081 Nov 35

Liver damage upon exposure to ionizing radiation, whether accidental or because of therapy can contribute to liver dysfunction. Currently, radiation therapy is used for various cancers including hepatocellular carcinoma; however, the treatment dose is limited by poor liver tolerance to radiation. Furthermore, reliable biomarkers to predict liver damage and associated side-effects are unavailable. Here, we investigated fibrinogen-like 1 (FGL1)-expression in the liver and plasma after radiation exposure. We found that 30 Gy of liver irradiation (IR) induced cell death including apoptosis, necrosis, and autophagy, with fibrotic changes in the liver occurring during the acute and subacute phase in mice. Moreover, FGL1 expression pattern in the liver following IR was associated with liver damage represented by injury-related proteins and oxidative stress markers. We confirmed the association between FGL1 expression and hepatocellular injury by exposing human hepatocytes to radiation. To determine its suitability, as a potential biomarker for radiation-induced liver injury, we measured FGL1 in the liver tissue and the plasma of mice following total body irradiation (TBI) or liver IR. In TBI, FGL1 showed the highest elevation in the liver compared to other major internal organs including the heart, lung, kidney, and intestine. Notably, plasma FGL1 showed good correlation with radiation dose by liver IR. Our data revealed that FGL1 upregulation indicates hepatocellular injury in response to IR. These results suggest that plasma FGL1 may represent a potential biomarker for acute and subacute radiation exposure to the liver.
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PMID:Plasma Fibrinogen-Like 1 as a Potential Biomarker for Radiation-Induced Liver Injury. 3148 41