Down's syndrome suppression of tumour growth and the role of the calcineurin inhibitor DSCR1

Kwan-Hyuck Baek, Alexander Zaslavsky, Ryan C. Lynch, Carmella Britt, Yoshiaki Okada, Richard J. Siarey, M. William Lensch, In-Hyun Park, Sam S. Yoon, Takashi Minami, Julie R. Korenberg, Judah Folkman, George Q. Daley, William C. Aird, Zygmunt Galdzicki and Sandra Ryeom ()
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Kwan-Hyuck Baek: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA
Alexander Zaslavsky: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA
Ryan C. Lynch: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA
Carmella Britt: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA
Yoshiaki Okada: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
Richard J. Siarey: Physiology and Genetic, Neuroscience, Molecular and Cellular Biology Program, School of Medicine, Uniformed Services University of the Health Services, Bethesda, Maryland 20814, USA
M. William Lensch: Children’s Hospital Boston, and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
In-Hyun Park: Children’s Hospital Boston, and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
Sam S. Yoon: Massachusetts General Hospital, Boston, Maryland 02114, USA
Takashi Minami: Research Center for Advanced Science and Technology, University of Tokyo, Tokyo, 153-8904, Japan
Julie R. Korenberg: The University of Utah, Salt Lake City, Utah 84108, USA
Judah Folkman: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA
George Q. Daley: Children’s Hospital Boston, and Dana-Farber Cancer Institute, Boston, Massachusetts 02115, USA
William C. Aird: Center for Vascular Biology Research, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02115, USA
Zygmunt Galdzicki: Physiology and Genetic, Neuroscience, Molecular and Cellular Biology Program, School of Medicine, Uniformed Services University of the Health Services, Bethesda, Maryland 20814, USA
Sandra Ryeom: Vascular Biology Program, Children’s Hospital Boston, Massachusetts 02115, USA

Nature, 2009, vol. 459, issue 7250, 1126-1130

Abstract: Down's syndrome and cancer Individuals with Down's syndrome are known to have a lower rate of certain solid cancers. New work from Baek et al. shows that a mouse model with an extra copy of the chromosome 21 gene Dscr1 (encoding Down syndrome critical region protein 1) exhibits decreased tumour growth due to reduced angiogenesis. They provide evidence that together with another chromosome 21 gene, Dyrk1a, a modest increase in Dscr1 expression limits angiogenesis by decreasing the activity of the calcineurin pathway. These data provide a mechanism for the reduced cancer incidence in Down's syndrome and identify the calcineurin signalling pathway, and its regulators DSCR1 and DYRK1A, as potential therapeutic targets in cancers arising in all individuals.

Date: 2009
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DOI: 10.1038/nature08062

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