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

Sandy F. Wotton, Karen Blyth, Anna Kilbey, Alma Jenkins, Anne Terry, Florence Bernardin-Fried, Alan D. Friedman, Euan W. Baxter, James C. Neil, Ewan R. Cameron

Research output: Contribution to journalArticle

Abstract

The mammalian Runx gene family (Runxl-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 marine 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.

Original languageEnglish (US)
Pages (from-to)5476-5486
Number of pages11
JournalOncogene
Volume23
Issue number32
DOIs
StatePublished - Jul 15 2004

Keywords

  • MEF
  • Oncogene
  • RUNX1
  • TGFβ
  • p53

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

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