UP-REGULATION OF MET BUT NOT NEURAL CELL-ADHESION MOLECULE EXPRESSIONBY THE PAX3-FKHR FUSION PROTEIN IN ALVEOLAR RHABDOMYOSARCOMA

The 2;13 chromosomal translocation in alveolar rhabdomyosarcoma genera tes the chimeric protein PAX3-FKHR, which is a powerful transcriptiona l activator, We hypothesize that PAX3-FKHR regulates downstream effect or genes involved in rhabdomyosarcoma tumorigenesis, We evaluated alte rations in expression of MET and neural cell adhesion molecule that we re proposed previously as downstream targets of wild-type PAX3. We use d a myogenic tumor cell culture system and rhabdomyosarcoma tumor spec imens to assess candidate gene expression in relationship to various P AX3-FKHR expression Levels. We demonstrate that the expression of MET, but not neural cell adhesion molecule, correlates significantly with PAX3-FKHR expression. These findings indicate that MET, which encodes a receptor involved in growth and motility signaling, is a downstream target of PAX3-FKHR in alveolar rhabdomyosarcoma.