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)

The promoter region of the human factor H gene was cloned and a 3 kb Eco RI fragment was sequenced. Primer extension and S1 nuclease analysis were used to determine the transcription start site, which was found to be 10-11 nucleotides upstream of the published cDNA sequence. No canonical TATA or CCAAT boxes were found in conjunction with this site. The sequence from the human H promoter region was compared to that from the mouse gene. There was a region of 800 bp that was 62.5% identical between the two sequences. The sequences of the two promoter regions were compared to a database of transcription factor binding sites. Five elements were identified that matched the consensus sequence 100% and were identical in the two promoter sequences. Promoter assays using the luciferase reporter gene demonstrated that this region contained a functional transcription start site and putative enhancer elements. U118-MG astroglioma cells and Hep3b hepatoma cells were incubated with various cytokines to measure effects on their factor H mRNA levels. Interferon-gamma (IFN-gamma), but not interleukin-1 (IL-1), tumour necrosis factor alpha (TNF-alpha) or IL-6, was able to increase the level of H mRNA in both cell lines.
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PMID:Characterization of the 5' flanking region of the human complement factor H gene. 901 Apr 94

A hepatitis B virus (HBV) integrant was cloned from the genomic DNA library of human hepatocellular carcinoma cell line, Hep3B. Sequence analysis of the restriction fragment bearing the virus-host junction revealed that its integration pattern was the common type, with the right junction located at the cohesive region. The open reading frame of the major viral surface antigen was intact with rearranged preS1 and core sequences. The X protein, although truncated, maintained the trans-activating activity to simian virus 40 enhancer/promoter. S1 nuclease mapping showed that 4.0-, 2.9-, and 2.2-kb HBV RNAs detected in Hep3B cells were transcribed from this integrant using preS2/S promoter. By somatic-cell hybrid mapping, the left and right cellular flanking sequences were assigned to chromosomes 13 and 4, respectively. The results of this study support the notion that integrated hepatitis B virus, resulting in chromosomal rearrangement as well as the production of the carboxy-terminal truncated X protein with trans-activating activity, is important for viral hepatocarcinogenesis.
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PMID:Characterization of hepatitis B virus integrant that results in chromosomal rearrangement. 962 85

Thrombopoietin (TPO) is predominantly expressed in the liver among various tissues that express TPO transcripts. To investigate the transcriptional regulation of the human TPO gene in the liver, we determined the major transcription initiation site by means of 5'-RACE and Northern blotting. From these analyses, we concluded that TPO gene transcription started at various points, and the transcription initiation sites of the human TPO gene were localized downstream, close to a point we determined by S1 nuclease mapping. The human TPO promoter region contains consensus sequences of GATA, Evi-1, and Ets binding sites. We used the hepatocellular carcinoma cell line, HepG2, that expresses TPO mRNA to analyze its promoter activity by transfecting various reporter plasmids containing a sequentially 5'-deleted human TPO promoter. Although GATA binding factors increased the promoter activity, their effect was independent of the GATA binding consensus sequence. On the other hand, Evi-1 did not affect transcription. Moreover, we defined the core promoter region, in which an Ets binding consensus sequence was located. The deletion or mutation of the Ets binding site resulted in a loss of the promoter activity. These results suggested that TPO is regulated by the Ets family of transcription factors.
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PMID:Gene expression and transcriptional regulation of thrombopoietin. 1101 15

An A-->T substitution in cDNA nucleotide 1197 (c.1197A/T) of the human phenylalanine hydroxylase (PAH) gene has been regarded as a silent mutation, because both the wild-type (GUA) and the mutant (GUU) alleles encode a valine residue at codon 399 (V399 V). The nucleotide c.1197 is located at the 3'-end of exon 11at position -3 of the exon-intron junction. To explore whether the substitution exerts any effects on the processing of the PAH mRNA, illegitimate PAH transcripts from lymphoblast cultures of a phenylketonuria (PKU) patient heterozygous for c.1197A/T were analyzed by the polymerase chain reaction following reverse-transcription (RT-PCR). mRNAs with an exon 11 deletion were revealed. Furthermore, by using an R408 W mutation in the paternal allele as a marker, sequence analysis of the RT-PCR products indicates that virtually all PAH transcripts from the maternal allele with the c. 1197A/T substitution do not contain exon 11. To address whether this substitution is the main determinant for exon skipping, PAH minigenes with or without the substitution were constructed and transfected to a human hepatoma cell line. Analysis of the transcription products by S1 nuclease mapping clearly indicated that such exon 11 skipping was directly associated with the c.1197A/T substitution. Thus, this study demonstrates that the c.1197A/T substitution in the PAH gene is not just a neutral polymorphism but a mutation that induces post-transcriptional skipping of exon 11 leading to a PKU phenotype.
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PMID:A silent mutation induces exon skipping in the phenylalanine hydroxylase gene in phenylketonuria. 1121 2


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