Neuroblastoma cell proliferation is sensitive to changes in levels of RUNX1 and RUNX3 protein

The Runt domain transcription factors Runx1 and Runx3 play crucial roles in dorsal root ganglion neurogenesis. Here we report that RUNX1 protein levels are maintained within a narrow range, despite highly variable levels of RUNX1 mRNA in neuroblastoma cell lines. Forced expression of the RUNX1 isoform AML1a (RUNX1/p27), a transcriptionally inactive competitive inhibitor, induces massive cell death, indicating that the function of RUNX1 is essential for neuroblastoma cell proliferation. Unexpectedly, over-expression of RUNX1 also induces cell death, as well as cell cycle arrest or differentiation. Furthermore, most neuroblastoma cell lines do not synthesize RUNX3 protein at detectable levels. Like RUNX1, exogenous expression also causes cell death, cell cycle arrest or differentiation. These results suggest that protein dosage of RUNX1 is critical for neuroblastoma cell growth and support a role for RUNX3 as a tumor suppressor in neuroblastoma.