Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/104463
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Type: Journal article
Title: Caspase-2 deficiency accelerates chemically induced liver cancer in mice
Author: Shalini, S.
Nikolic, A.
Wilson, C.
Puccini, J.
Sladojevic, N.
Finnie, J.
Dorstyn, L.
Kumar, S.
Citation: Cell Death and Differentiation, 2016; 23(10):1727-1736
Publisher: Nature Publishing Group
Issue Date: 2016
ISSN: 1350-9047
1476-5403
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Responsibility: 
S Shalini, A Nikolic, CH Wilson, J Puccini, N Sladojevic, J Finnie, L Dorstyn and S Kumar
Abstract: Aberrant cell death/survival has a critical role in the development of hepatocellular carcinoma (HCC). Caspase-2, a cell death protease, limits oxidative stress and chromosomal instability. To study its role in reactive oxygen species (ROS) and DNA damage-induced liver cancer, we assessed diethylnitrosamine (DEN)-mediated tumour development in caspase-2-deficient (Casp2−/−) mice. Following DEN injection in young animals, tumour development was monitored for 10 months. We found that DEN-treated Casp2−/− mice have dramatically elevated tumour burden and accelerated tumour progression with increased incidence of HCC, accompanied by higher oxidative damage and inflammation. Furthermore, following acute DEN injection, liver injury, DNA damage, inflammatory cytokine release and hepatocyte proliferation were enhanced in mice lacking caspase-2. Our study demonstrates for the first time that caspase-2 limits the progression of tumourigenesis induced by an ROS producing and DNA damaging reagent. Our findings suggest that after initial DEN-induced DNA damage, caspase-2 may remove aberrant cells to limit liver damage and disease progression. We propose that Casp2−/− mice, which are more susceptible to genomic instability, are limited in their ability to respond to DNA damage and thus carry more damaged cells resulting in accelerated tumourigenesis.
Keywords: liver cancer; mice
Rights: & © 2016 Macmillan Publishers Limited, part of Springer Nature. All rights reserved
RMID: 0030063120
DOI: 10.1038/cdd.2016.81
Grant ID: http://purl.org/au-research/grants/nhmrc/1021456
http://purl.org/au-research/grants/nhmrc/1073771
http://purl.org/au-research/grants/nhmrc/1002863
http://purl.org/au-research/grants/nhmrc/1103006
Appears in Collections:Medicine publications

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