title: The RUNX Genes as Conditional Oncogenes: Insights from Retroviral Targeting and Mouse Models.
abstract: 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.
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK. James.Neil@glasgow.ac.uk.
authors.forename: James C
authors.initials: JC
authors.lastname: Neil
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Gilroy
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
authors.forename: Gillian
authors.initials: G
authors.lastname: Borland
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
authors.forename: Jodie
authors.initials: J
authors.lastname: Hay
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
authors.forename: Anne
authors.initials: A
authors.lastname: Terry
authors.affiliation: Molecular Oncology Laboratory, Centre for Virus Research, University of Glasgow, Bearsden, Glasgow, G61 1QH, UK.
authors.forename: Anna
authors.initials: A
authors.lastname: Kilbey
mesh_terms: D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D050657:Core Binding Factor alpha Subunits / Q000235:genetics*; D004195:Disease Models, Animal; D006801:Humans; D051379:Mice; D009369:Neoplasms / Q000235:genetics*; D009857:Oncogenes / Q000235:genetics*; D012190:Retroviridae / Q000254:growth & development*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
chemical_list: D050657:Core Binding Factor alpha Subunits; D016159:Tumor Suppressor Protein p53
keywords: Cancer; Lymphoma; Oncogene; Retroviral mutagenesis; Senescence; Tumour suppressor