RUNX1 transformation of primary embryonic fibroblasts is revealed in the absence of p53

Wotton, S. F., Blyth, K. , Kilbey, A., Jenkins, A., Terry, A., Bernardin-Fried, F., Friedman, A. D., Baxter, E. W., Neil, J. C. and Cameron, E. R. (2004) RUNX1 transformation of primary embryonic fibroblasts is revealed in the absence of p53. Oncogene, 23(32), pp. 5476-5486. (doi: 10.1038/sj.onc.1207729) (PMID:15133495)

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Abstract

The mammalian Runx gene family (Runx1–3) are transcription factors that play essential, lineage-specific roles in development. A growing body of evidence implicates these genes as mutational targets in cancer where, in different contexts, individual family members have been reported to act as tumour suppressors, dominant oncogenes or mediators of metastasis. We are exploring these paradoxical observations by ectopic expression of RUNX genes in primary murine embryonic fibroblasts where, in common with a number of other dominant oncogenes, RUNX1 induces senescence-like growth arrest in the presence of an intact p19ARF-p53 pathway. We now report that, in MEFs lacking functional p53, RUNX1 has apparently prooncogenic effects on cell growth that include cytoskeletal reorganization, reduced contact inhibition at confluence and accelerated tumour expansion in vivo. On the other hand, RUNX1 conferred no obvious growth advantage at low cell density and actually delayed entry of primary MEFs into S phase. We also found that ectopic RUNX1 interferes with the morphological and growth responses of p53-null MEFs to TGFβ indicating that these effects are mediated by overlapping pathways. These observations help to elucidate the context-dependent consequences of loss and gain of Runx activity.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Wotton, Dr Sandra and Blyth, Professor Karen and Cameron, Professor Ewan and Kilbey, Dr Anna and Neil, Professor James and Terry, Mrs Anne
Authors: Wotton, S. F., Blyth, K., Kilbey, A., Jenkins, A., Terry, A., Bernardin-Fried, F., Friedman, A. D., Baxter, E. W., Neil, J. C., and Cameron, E. R.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
College of Medical Veterinary and Life Sciences > School of Veterinary Medicine
College of Medical Veterinary and Life Sciences > Institute of Cancer Sciences
Journal Name:Oncogene
Publisher:Nature Publishing Group
ISSN:0950-9232
ISSN (Online):1476-5594
Published Online:10 May 2004

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