Expression of N-myc and MRP genes and their relationship to N-myc gene dosage and tumor formation in a murine neuroblastoma model

Background. Although the association between N-myc gene amplification and p oor clinical outcome in neuroblastoma is well established, the mechanism by which amplification influences prognosis is not well defined. Procedure. W e used a human N-myc transgenic mouse model to investigate the role of N-my c in neuroblastoma, including its relationship to the multidrug-resistance- associated protein (MRP) gene. We developed a rapid realtime PCR method to distinguish homozygous and hemizygous N-myc mice that is comparable to Sout hern analysis. Results. A highly significant correlation (P < 0.0001) betwe en N-myc and MRP expression was demonstrated in murine tumors. Amplificatio n of the transgene was observed in the majority of tumors, high lighting th e clinical relevance of this model. However, no correlation between N-myc e xpression and transgene dosage or tumor latency was observed. Conclusions. The data suggest that increased N-myc dosage contributes to increased tumor incidence and decreased latency by mechanisms independent of N-myc express ion. (C) 2000 Wiley-Liss, Inc.