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New model systems provide insights into Myc-induced transformation

Oncogene volume 30, pages 3727–3734 (2011)Cite this article

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Abstract

The ability of Myc to promote cellular transformation is well established; however, a better understanding of the mechanisms through which Myc mediates tumorigenesis is essential for the development of therapeutic approaches to target this potent oncoprotein. Structure–function studies in rodent fibroblast cells have provided the basis for much of our current understanding of these mechanisms. To build on these approaches, we have characterized three novel human cell line models of Myc-dependent transformation: MCF10A, SH-EP Tet21/N-Myc, and LF1/TERT/LT/ST cells. We have also evaluated Myc family proteins (c-Myc and L-Myc), a naturally occurring isoform of Myc (MycS), and a set of N-terminal domain mutants (ΔMBII, W135E, T58A) for their ability to promote anchorage-independent growth in these models. Taken together, these results provide the field with three new human cell-based models to study Myc activity, highlight the importance of cellular context, and challenge the paradigm that the ability of Myc to promote tumorigenesis is exclusively MBII-dependent.

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Acknowledgements

We would like to acknowledge technical assistance from Ms Caitlin Latimer. We thank the members of the Penn Lab for helpful discussions and critical review of this manuscript. This research was funded by a grant from the Canadian Cancer Society Research Institute (LZP), an Ontario Graduate Scholarship (AS), and a Canadian Breast Cancer Foundation Ontario Region Doctoral Fellowship (ARW). Additional support was provided by the Ontario Ministry of Health and Long Term Care. The views expressed do not necessarily reflect those of the OMOHLTC.

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  1. A R Wasylishen and A Stojanova: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada

    A R Wasylishen, A Stojanova, S Oliveri, A C Rust, A D Schimmer & L Z Penn

  2. Ontario Cancer Institute, Campbell Family Institute for Cancer Research, Toronto, Ontario, Canada

    A R Wasylishen, A Stojanova, S Oliveri, A C Rust, A D Schimmer & L Z Penn

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  1. A R Wasylishen
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  2. A Stojanova
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  3. S Oliveri
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  4. A C Rust
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  5. A D Schimmer
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Correspondence to L Z Penn.

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Wasylishen, A., Stojanova, A., Oliveri, S. et al. New model systems provide insights into Myc-induced transformation. Oncogene 30, 3727–3734 (2011). https://doi.org/10.1038/onc.2011.88

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