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https://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/ |
DOI: | 10.1038/cddis.2014.342 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1043057 http://purl.org/au-research/grants/nhmrc/1002863 |
Published version: | http://dx.doi.org/10.1038/cddis.2014.342 |
Appears in Collections: | Aurora harvest 2 Medicine publications |
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hdl_94378.pdf | Published version | 3.56 MB | Adobe PDF | View/Open |
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