| A novel mouse model of hepatocarcinogenesis triggered by AID causing deleterious p53 mutations. | |
| | |
MedLine Citation:
|
PMID: 18997814 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Activation-induced cytidine deaminase (AID), the only enzyme that is known to be able to induce mutations in the human genome, is required for somatic hypermutation and class-switch recombination in B lymphocytes. Recently, we showed that AID is implicated in the pathogenesis of human cancers including hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC). In this study, we established a new AID transgenic mouse model (TNAP-AID) in which AID is expressed in cells producing tissue-nonspecific alkaline phosphatase (TNAP), which is a marker of primordial germ cells and immature stem cells, including ES cells. High expression of TNAP was found in the liver of the embryos and adults of TNAP-AID mice. HCC developed in 27% of these mice at the age of approximately 90 weeks. The HCC that developed in TNAP-AID mice expressed alpha-fetoprotein and had deleterious mutations in the tumour suppressor gene Trp53, some of which corresponded to those found in human cancer. In conclusion, TNAP-AID is a mouse model that spontaneously develops HCC, sharing genetic and phenotypic features with human HCC, which develops in the inflamed liver as a result of the accumulation of genetic changes. |
| | |
Authors:
|
A Takai; T Toyoshima; M Uemura; Y Kitawaki; H Marusawa; H Hiai; S Yamada; I M Okazaki; T Honjo; T Chiba; K Kinoshita |
Related Documents
:
|
6573384 - Research on craniofacial genetics and developmental biology: implications for the futur... 11645824 - The intellectual basis for latino aids policy: towards the humanities and health policy. 18695214 - Colloquium paper: where does biodiversity go from here? a grim business-as-usual foreca... 6455744 - 1980 volvo award in biomechanics. measurement of the distribution of axial stress on th... 6973414 - The schistosomiasis problem in the world: results of a who questionnaire survey. 22557014 - Role of achara rasayana and sadvrta in the prevention of aids. |
Publication Detail:
|
Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-10 |
Journal Detail:
|
Title: Oncogene Volume: 28 ISSN: 1476-5594 ISO Abbreviation: Oncogene Publication Date: 2009 Jan |
Date Detail:
|
Created Date: 2009-01-30 Completed Date: 2009-02-17 Revised Date: - |
Medline Journal Info:
|
Nlm Unique ID: 8711562 Medline TA: Oncogene Country: England |
Other Details:
|
Languages: eng Pagination: 469-78 Citation Subset: IM |
Affiliation:
|
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Aging
/
genetics,
metabolism Alkaline Phosphatase / genetics, metabolism* Animals Antigens, Differentiation / genetics, metabolism B-Lymphocytes / metabolism, pathology Carcinoma, Hepatocellular / genetics, metabolism*, pathology Cytidine Deaminase / genetics, metabolism* Disease Models, Animal Embryo, Mammalian / metabolism, pathology Gene Expression Regulation, Neoplastic* / genetics Genome, Human / genetics Hepatitis / genetics, metabolism, pathology Humans Liver / metabolism, pathology Liver Neoplasms / genetics, metabolism*, pathology Mice Mice, Transgenic Organ Specificity / genetics Sequence Deletion / genetics Somatic Hypermutation, Immunoglobulin / genetics Stem Cells / metabolism, pathology Tumor Suppressor Protein p53 / genetics, metabolism* alpha-Fetoproteins / genetics, metabolism |
| Chemical | |
Reg. No./Substance:
|
0/Antigens, Differentiation; 0/Tumor Suppressor Protein p53; 0/alpha-Fetoproteins; EC 3.1.3.1/Alkaline Phosphatase; EC 3.5.4.-/AICDA (activation-induced cytidine deaminase); EC 3.5.4.5/Cytidine Deaminase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Activation of the transient receptor potential vanilloid-1 (TRPV1) channel opens the gate for pain r...
Next Document: Hedgehog signaling promotes the degradation of tumor suppressor Sufu through the ubiquitin-proteasom...