Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis
- University of Colorado School of Medicine, United States
- Duke University Medical Center, United States
Abstract
The mechanism for Myc-induced genetic instability is not well understood. Here we show that sublethal activation of Caspase-3 plays an essential, facilitative role in Myc-induced genomic instability and oncogenic transformation. Overexpression of Myc resulted in increased numbers of chromosome aberrations and γH2AX foci in non-transformed MCF10A human mammary epithelial cells. However, such increases were almost completely eliminated in isogenic cells with CASP3 gene ablation. Furthermore, we show that endonuclease G, an apoptotic nuclease downstream of Caspase-3, is directly responsible Myc-induced genetic instability. Genetic ablation of either CASP3 or ENDOG prevented Myc-induced oncogenic transformation of MCF10A cells. Taken together, we believe that Caspase-3 plays a critical, unexpected role in mediating Myc-induced genetic instability and transformation in mammalian cells.
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Author details
Funding
National Cancer Institute (CA155720)
- Chuan-Yuan Li
National Institute of Environmental Health Sciences (ES024015)
- Chuan-Yuan Li
National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR066527)
- Chuan-Yuan Li
National Cancer Institute (2008852)
- Chuan-Yuan Li
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: The animal experiments conducted in this study were approved by the Duke University Institutional Animal Use and Care Committee (IACUC) with the protocol number A195-14-98.
Copyright
© 2017, Cartwright et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Essential roles of Caspase-3 in facilitating Myc-induced genetic instability and carcinogenesis
eLife 6:e26371.
https://doi.org/10.7554/eLife.26371
