期刊论文详细信息
BMC Cell Biology
MXD3 regulation of DAOY cell proliferation dictated by time course of activation
Research Article
Kit S Lam1  Elva Dίaz2  Gustavo A Barisone2  Tin Ngo3 
[1] Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA;Department of Pharmacology, UC Davis School of Medicine, 451 Health Sciences Drive, 3503 GBSF, 95616, Davis, CA, USA;Department of Pharmacology, UC Davis School of Medicine, 451 Health Sciences Drive, 3503 GBSF, 95616, Davis, CA, USA;Department of Biochemistry and Molecular Medicine, University of California Davis School of Medicine, Davis, CA, USA;
关键词: MXD3;    Proliferation;    Medulloblastoma;    DAOY;   
DOI  :  10.1186/1471-2121-15-30
 received in 2013-12-03, accepted in 2014-07-02,  发布年份 2014
来源: Springer
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【 摘 要 】

BackgroundMXD3 is a basic-helix-loop-helix-leucine-zipper transcription factor involved in cellular proliferation. In previous studies we demonstrated that knock-down of MXD3 in the human medulloblastoma cell line DAOY resulted in decreased proliferation. Surprisingly, overexpression of MXD3 in DAOY cells also decreased proliferation and increased cell death, suggesting that persistent expression of MXD3 triggers an apoptotic response, perhaps as a fail-safe mechanism. To investigate this apparent paradox in detail we developed a tamoxifen inducible system to analyze the temporal effects of MXD3 in the proliferation and transcriptional response of DAOY cells upon acute induction compared with long-term expression of MXD3.ResultsWe find that acute induction of MXD3 initially promotes cell cycle progression as assessed by a transient increase in bromodeoxyuridine incorporation. However, persistent induction of MXD3 ultimately results in decreased proliferation based on cell counts. Finally, with microarray expression profiling and gene ontology analysis we identify several major pathways enriched in response to acute (immune response, apoptosis, cell cycle) versus persistent (cell adhesion) MXD3 activation.ConclusionsIn this study, we demonstrate that acute MXD3 activation results in a transient increase in cell proliferation while persistent activation of MXD3 eventually results in an overall decrease in cell number, suggesting that the time course of MXD3 expression dictates the cellular outcome. Microarray expression profiling and gene ontology analysis indicate that MXD3 regulates distinct genes and pathways upon acute induction compared with persistent expression, suggesting that the cellular outcome is specified by changes in MXD3 transcriptional program in a time-dependent manner.

【 授权许可】

Unknown   
© Ngo et al.; licensee BioMed Central Ltd. 2014. This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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