Linked Life Data

17066440

Source:http://linkedlifedata.com/resource/pubmed/id/17066440

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2006-12-5
pubmed:abstractText
Activation-induced cytidine deaminase (AID) plays a role as a genome mutator in activated B cells, and inappropriate expression of AID has been implicated in the immunopathological phenotype of human B-cell malignancies. Notably, we found that the transgenic mice overexpressing AID developed lung adenocarcinoma and hepatocellular carcinoma (HCC), suggesting that ectopic expression of AID can lead to tumorigenesis in epithelial tissues as well. To examine the involvement of AID in the development of human HCC, we analyzed the AID expression and its correlation with mutation frequencies of the p53 gene in liver tissues from 51 patients who underwent resection of primary HCCs. The specific expression, inducibility by cytokine stimulation and mutagenic activity of AID were investigated in cultured human hepatocytes. Only trace amounts of AID transcripts were detected in the normal liver; however, endogenous AID was significantly upregulated in both HCC and surrounding noncancerous liver tissues with underlying chronic hepatitis or liver cirrhosis (p < 0.05). Most liver tissues with underlying chronic inflammation with endogenous AID upregulation already contained multiple genetic changes in the p53 gene. In both hepatoma cell lines and cultured human primary hepatocytes, the expression of AID was substantially induced by TGF-beta stimulation. Aberrant activation of AID in hepatocytes resulted in accumulation of multiple genetic alterations in the p53 gene. Our findings suggest that the aberrant expression of AID is observed in human hepatocytes with several pathological settings, including chronic liver disease and HCC, which might enhance the genetic susceptibility to mutagenesis leading to hepatocarcinogenesis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0020-7136
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
120
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
469-76
pubmed:dateRevised
2007-7-24
pubmed:meshHeading
pubmed-meshheading:17066440-Adult, pubmed-meshheading:17066440-Aged, pubmed-meshheading:17066440-Aged, 80 and over, pubmed-meshheading:17066440-Amino Acid Sequence, pubmed-meshheading:17066440-Base Sequence, pubmed-meshheading:17066440-Carcinoma, Hepatocellular, pubmed-meshheading:17066440-Cell Line, Tumor, pubmed-meshheading:17066440-Cells, Cultured, pubmed-meshheading:17066440-Cytidine Deaminase, pubmed-meshheading:17066440-Enzyme Activation, pubmed-meshheading:17066440-Female, pubmed-meshheading:17066440-Gene Expression Regulation, Enzymologic, pubmed-meshheading:17066440-Gene Expression Regulation, Neoplastic, pubmed-meshheading:17066440-Hepatitis, Viral, Human, pubmed-meshheading:17066440-Hepatocytes, pubmed-meshheading:17066440-Humans, pubmed-meshheading:17066440-Immunoblotting, pubmed-meshheading:17066440-Liver Neoplasms, pubmed-meshheading:17066440-Male, pubmed-meshheading:17066440-Middle Aged, pubmed-meshheading:17066440-Mutation, pubmed-meshheading:17066440-RNA, Messenger, pubmed-meshheading:17066440-Reverse Transcriptase Polymerase Chain Reaction, pubmed-meshheading:17066440-Transforming Growth Factor beta, pubmed-meshheading:17066440-Tumor Suppressor Protein p53
pubmed:year
2007
pubmed:articleTitle
Expression of activation-induced cytidine deaminase in human hepatocytes during hepatocarcinogenesis.
pubmed:affiliation
Department of Gastroenterology and Hepatology, Kyoto University Graduate School of Medicine, Kyoto, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't