The RUNX genes as conditional oncogenes: insights from retroviral targeting and mouse models

Neil, J. C. , Gilroy, K., Borland, G., Hay, J. , Terry, A. and Kilbey, A. (2017) The RUNX genes as conditional oncogenes: insights from retroviral targeting and mouse models. In: Groner, Y., Ito, Y., Liu, P., Neil, J. C., Speck, N. A. and van Wijnen, A. (eds.) RUNX Proteins in Development and Cancer. Series: Advances in experimental medicine and biology (962). Springer, pp. 247-264. ISBN 9789811032318 (doi: 10.1007/978-981-10-3233-2_16)

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The observation that the Runx genes act as targets for transcriptional activation by retroviral insertion identified a new family of dominant oncogenes. However, it is now clear that Runx genes are 'conditional' oncogenes whose over-expression is growth inhibitory unless accompanied by another event such as concomitant over-expression of MYC or loss of p53 function. Remarkably, while the oncogenic activities of either MYC or RUNX over-expression are suppressed while p53 is intact, the combination of both neutralises p53 tumour suppression in vivo by as yet unknown mechanisms. Moreover, there is emerging evidence that endogenous, basal RUNX activity is important to maintain the viability and proliferation of MYC-driven lymphoma cells. There is also growing evidence that the human RUNX genes play a similar conditional oncogenic role and are selected for over-expression in end-stage cancers of multiple types. Paradoxically, reduced RUNX activity can also predispose to cell immortalisation and transformation, particularly by mutant Ras. These apparently conflicting observations may be reconciled in a stage-specific model of RUNX involvement in cancer. A question that has yet to be fully addressed is the extent to which the three Runx genes are functionally redundant in cancer promotion and suppression.

Item Type:Book Sections
Keywords:Cancer, lymphoma, oncogene, retroviral mutagenesis, senescence, tumour suppressor.
Glasgow Author(s) Enlighten ID:Neil, Professor James and Kilbey, Dr Anna and Borland, Dr Gillian and Hay, Dr Jodie and Gilroy, Dr Kathryn and Terry, Mrs Anne
Authors: Neil, J. C., Gilroy, K., Borland, G., Hay, J., Terry, A., and Kilbey, A.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Published Online:16 March 2017

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