Please use this identifier to cite or link to this item:
|Title:||Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice||Authors:||Teoh, N.C.
|Issue Date:||Jun-2008||Citation:||Teoh, N.C., Yock, Y.D., Swisshelm, K., Lehman, S., Wright, J.H., Haque, J., Gu, Y., Fausto, N. (2008-06). Defective DNA strand break repair causes chromosomal instability and accelerates liver carcinogenesis in mice. Hepatology 47 (6) : 2078-2088. ScholarBank@NUS Repository. https://doi.org/10.1002/hep.22194||Abstract:||Chromosomal instability is a characteristic feature of hepatocellular carcinoma (HCC) but its origin and role in liver carcinogenesis are undefined. We tested whether a defect in the nonhomologous end-joining (NHEJ) DNA repair gene Ku70 was associated with chromosomal abnormalities and enhanced liver carcinogenesis. Male Ku70 NHEJ-deficient (Ku70-/-), heterozygote (Ku70 +/-), and wild-type (WT) mice were injected with diethylnitrosamine (DEN), a liver carcinogen, at age 15 days. Animals were killed at 3, 6, and 9 months for assessment of tumorigenesis and hepatocellular proliferation. For karyotype analysis, primary liver tumor cell cultures were prepared from HCCs arising in Ku70 mice of all genotypes. Compared to WT littermates, Ku70-/- mice injected with DEN displayed accelerated HCC development. Ku70-/- HCCs harbored clonal increases in numerical and structural aberrations of chromosomes 4, 5, 7, 8, 10, 14, and 19, many of which recapitulated the spectrum of equivalent chromosomal abnormalities observed in human HCC. Ku70-/- HCCs showed high proliferative activity with increased cyclin D1 and proliferating cell nuclear antigen expression, Aurora A kinase activity, enhanced ataxia telangiectasia mutated kinase and ubiquitination, and loss of p53 via proteasomal degradation, features which closely resemble those of human HCC. Conclusion: These findings demonstrate that defects in the NHEJ DNA repair pathway may participate in the disruption of cell cycle checkpoints leading to chromosomal instability and accelerated development of HCC. Copyright © 2008 by the American Association for the Study of Liver Diseases.||Source Title:||Hepatology||URI:||http://scholarbank.nus.edu.sg/handle/10635/129767||ISSN:||02709139||DOI:||10.1002/hep.22194|
|Appears in Collections:||Staff Publications|
Show full item record
Files in This Item:
There are no files associated with this item.
checked on Nov 13, 2019
WEB OF SCIENCETM
checked on Nov 13, 2019
checked on Nov 8, 2019
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.