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

Wotton, S., Terry, A., Kilbey, A., Jenkins, A., Herzyk, P. , Cameron, E. and Neil, J.C. (2008) Gene array analysis reveals a common Runx transcriptional programme controlling cell adhesion and survival. Oncogene, 27(44), pp. 5856-5866. (doi: 10.1038/onc.2008.195)

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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 afterfurther 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 CBFBMYH11) 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 andRgs2) rather than impose constitutive repression. These results elucidate the oncogenic potential of the Runx family and reveal novel targets for therapeutic inhibition.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Cameron, Professor Ewan and Neil, Professor James and Mcdonald, Mrs Alma and Herzyk, Dr Pawel and Kilbey, Dr Anna and Terry, Mrs Anne
Authors: Wotton, S., Terry, A., Kilbey, A., Jenkins, A., Herzyk, P., Cameron, E., and Neil, J.C.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:16 June 2008

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