Please use this identifier to cite or link to this item: http://hdl.handle.net/2440/94378
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Type: Journal article
Title: An unexpected role for caspase-2 in neuroblastoma
Author: Dorstyn, L.
Puccini, J.
Nikolic, A.
Shalini, S.
Wilson, C.
Norris, M.
Haber, M.
Kumar, S.
Citation: Cell Death and Disease, 2014; 5(8):e1383-1-e1383-9
Publisher: Nature
Issue Date: 2014
ISSN: 2041-4889
2041-4889
Statement of
Responsibility: 
L Dorstyn, J Puccini, A Nikolic, S Shalini, CH Wilson, MD Norris, M Haber and S Kumar
Abstract: Caspase-2 has been implicated in various cellular functions, including cell death by apoptosis, oxidative stress response, maintenance of genomic stability and tumor suppression. The loss of the caspase-2 gene (Casp2) enhances oncogene-mediated tumorigenesis induced by E1A/Ras in athymic nude mice, and also in the Eμ-Myc lymphoma and MMTV/c-neu mammary tumor mouse models. To further investigate the function of caspase-2 in oncogene-mediated tumorigenesis, we extended our studies in the TH-MYCN transgenic mouse model of neuroblastoma. Surprisingly, we found that loss of caspase-2 delayed tumorigenesis in the TH-MYCN neuroblastoma model. In addition, tumors from TH-MYCN/Casp2(-/-) mice were predominantly thoracic paraspinal tumors and were less vascularized compared with tumors from their TH-MYCN/Casp2(+/+) counterparts. We did not detect any differences in the expression of neuroblastoma-associated genes in TH-MYCN/Casp2(-/-) tumors, or in the activation of Ras/MAPK signaling pathway that is involved in neuroblastoma progression. Analysis of expression array data from human neuroblastoma samples showed a correlation between low caspase-2 levels and increased survival. However, caspase-2 levels correlated with clinical outcome only in the subset of MYCN-non-amplified human neuroblastoma. These observations indicate that caspase-2 is not a suppressor in MYCN-induced neuroblastoma and suggest a tissue and context-specific role for caspase-2 in tumorigenesis.
Keywords: Animals; Mice, Inbred C57BL; Mice, Transgenic; Mice, Knockout; Humans; Mice; Neuroblastoma; Disease Models, Animal; ras Proteins; Mitogen-Activated Protein Kinases; Signal Transduction; Caspase 2; Kaplan-Meier Estimate
Rights: Cell Death and Disease is an open-access journal published by Nature Publishing Group. This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/3.0/
RMID: 0030022845
DOI: 10.1038/cddis.2014.342
Grant ID: http://purl.org/au-research/grants/nhmrc/1043057
http://purl.org/au-research/grants/nhmrc/1002863
Appears in Collections:Medicine publications

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