Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01034 (cystatin C)
 3,397 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of the c-myc gene has previously been shown to be elevated and deregulated in the human hepatoma cell line Hep G2 (B. E. Huber and S. S. Thorgeirsson, Cancer Res., 47: 3414-3420, 1987). We now report that the Hep G2 N-ras gene is activated to a dominant-acting, transforming gene by a missense mutation in codon 61. Hep G2 DNA produced transformed foci when transfected into NIH 3T3 cells. Subsequent to a secondary round of transfection, Southern blot analysis of tumorigenic NIH 3T3 foci demonstrated the presence of human N-ras sequences. Nucleotide sequence analysis of one Hep G2 N-ras allele demonstrated that codons 12, 13, and 59 were normal and that codon 61 had a missense mutation (CAA to CTA). This mutation results in the incorporation of leucine instead of glutamine at residue 61 of the N-ras gene product, p21. N-ras sequences were amplified by the polymerase chain reaction from both Hep G2 genomic DNA and Hep G2 complementary DNA. Analysis of the amplified sequences demonstrated that only one Hep G2 N-ras allele exhibited the codon 61 mutation and that both the mutant and normal alleles were transcribed. Northern blot analysis demonstrated equivalent steady-state levels of N-ras transcripts in Hep G2 cells and normal human liver. The steady-state levels of N-ras and ornithine decarboxylase transcripts were positively correlated suggesting a positive relationship between N-ras expression and the replication rate of Hep G2 cells. c-Ki-ras and c-Ha-ras transcripts were not detected in either Hep G2 cells or normal human liver. Immunoprecipitation experiments using the monoclonal antibody Y13-259 demonstrated the presence of p21 in Hep G2 cells. Expression of a dominant-acting, transforming N-ras gene, in conjunction with the altered regulation of the c-myc gene, documents two important genetic lesions that could be responsible for the transformed phenotype of Hep G2 cells.
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PMID:Characterization of a transforming N-ras gene in the human hepatoma cell line Hep G2: additional evidence for the importance of c-myc and ras cooperation in hepatocarcinogenesis. 215 25

Ornithine decarboxylase (ODC) plays an important role in cell growth, and its activity is regulated by many mechanisms. The biochemical characteristics of ODC in malignant cells differ from those of ODC in normal cells. To determine whether novel changes occur in ODC in neoplastic tissue, we compared the nucleotide sequence of ODC cDNA obtained from human hepatoma tissue as determined by reverse transcriptase-PCR with that of ODC cDNA obtained from nontumorous tissue in the same patients. There were three point mutations accompanied by replacements of amino acids in hepatoma tissue with other amino acids or a stop codon. In one poorly differentiated hepatoma, codon 415, CAA was converted to TAA, resulting in replacement of Gln-415 by a stop codon. The mutated ODC protein produced by translation in a reticulocyte-lysate protein synthesizing system was truncated and stabilized in an ATP antizyme-dependent degradation system. These findings suggest that formation of a truncated and stabilized ODC protein due to point mutation is one reason why ODC activity is high in human hepatoma tissue.
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PMID:Point mutation of ornithine decarboxylase gene in human hepatocellular carcinoma. 762 54