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Up-Regulation of MET but not Neural Cell Adhesion Molecule Expression by the PAX3-FKHR Fusion Protein in Alveolar Rhabdomyosarcoma¹

Division of Oncology, The Children's Hospital of Philadelphia [J. P. G.] and Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine [J. P. G., R. J. D., J. L. B., L. E. N., F. G. B.], Philadelphia, Pennsylvania 19104

The 2;13 chromosomal translocation in alveolar rhabdomyosarcoma generates the chimeric protein PAX3-FKHR, which is a powerful transcriptional activator. We hypothesize that PAX3-FKHR regulates downstream effector genes involved in rhabdomyosarcoma tumorigenesis. We evaluated alterations in expression of MET and neural cell adhesion molecule that were proposed previously as downstream targets of wildtype PAX3. We used a myogenic tumor cell culture system and rhabdomyosarcoma tumor specimens to assess candidate gene expression in relationship to various PAX3-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.

¹ This work was supported in part by NIH Grants CA64202 and CA71838 (to F. G. B.) and by NIH Grants T32-CA09615 and K12-CA76931 (to J. P. G.).

² Present address: Department of Pathology, Baylor College of Medicine, Houston, TX 77030.

³ To whom requests for reprints should be addressed, at Department of Pathology and Laboratory Medicine, University of Pennsylvania School of Medicine, 37th Street and Hamilton Walk, Philadelphia, PA 19104-6082.

Received 5/ 5/98. Accepted 6/30/98.

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