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  • Oncogenomics
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Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival

Oncogene volume 27, pages 5856–5866 (2008)Cite this article

Abstract

The Runx genes are important in development and cancer, where they can act either as oncogenes or tumour suppressors. We compared the effects of ectopic Runx expression in established fibroblasts, where all three genes produce an indistinguishable phenotype entailing epithelioid morphology and increased cell survival under stress conditions. Gene array analysis revealed a strongly overlapping transcriptional signature, with no examples of opposing regulation of the same target gene. A common set of 50 highly regulated genes was identified after further filtering on regulation by inducible RUNX1-ER. This set revealed a strong bias toward genes with annotated roles in cancer and development, and a preponderance of targets encoding extracellular or surface proteins, reflecting the marked effects of Runx on cell adhesion. Furthermore, in silico prediction of resistance to glucocorticoid growth inhibition was confirmed in fibroblasts and lymphoid cells expressing ectopic Runx. The effects of fibroblast expression of common RUNX1 fusion oncoproteins (RUNX1-ETO, TEL-RUNX1 and CBFB-MYH11) were also tested. Although two direct Runx activation target genes were repressed (Ncam1 and Rgc32), the fusion proteins appeared to disrupt the regulation of downregulated targets (Cebpd, Id2 and Rgs2) rather than impose constitutive repression. These results elucidate the oncogenic potential of the Runx family and reveal novel targets for therapeutic inhibition.

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Acknowledgements

We thank Scott Hiebert (Vanderbilt Cancer Centre, TN, USA) for RUNX1/ETO and CBFB-MYH11 plasmids, Alan Friedman (Johns Hopkins University, MD, USA) for the AML-ER plasmid and Olivier Bernard (INSERM, Paris, France) for the TEL/RUNX1 construct. We are grateful to Torsten Schaller for the murine Runx3 cDNA and to Monica Stewart and Karen Blyth for helpful comments. This work was supported by a programme grant from Cancer Research, UK, and the Leukaemia Research Fund of Great Britain.

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Authors and Affiliations

  1. Molecular Oncology Laboratory, Faculty of Veterinary Medicine, Institute of Comparative Medicine, University of Glasgow, Glasgow, Scotland

    S Wotton, A Terry, A Kilbey, A Jenkins, E Cameron & J C Neil

  2. Sir Henry Wellcome Functional Genomics Facility, Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, Scotland

    P Herzyk

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  1. S Wotton
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Correspondence to S Wotton or J C Neil.

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Wotton, S., Terry, A., Kilbey, A. et al. Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival. Oncogene 27, 5856–5866 (2008). https://doi.org/10.1038/onc.2008.195

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