cDNA microarrays detect activation of a myogenic transcription program by the PAX3-FKHR fusion oncogene

Alveolar rhabdomyosarcoma is an aggressive pediatric cancer of striated mus cle characterized in 60 % of cases by a t(2;13)(q35;q14). This results in t he fusion of PAX3, a developmental transcription factor required for limb m yogenesis, with FKHR, a member of the forkhead family of transcription fact ors. The resultant PAX3-FKHR gene possesses transforming properties; howeve r, the effects of this chimeric oncogene on gene expression are largely unk nown. To investigate the actions of these transcription factors, both Pax3 and PAX3-FKHR were introduced into NIH 3T3 cells, and the resultant gene ex pression changes were analyzed with a murine cDNA microarray containing 2,2 25 elements. We found that PAX3-FKHR but not PAX3 activated a myogenic tran scription program including the induction of transcription factors MyoD, My ogenin, Six1, and Slug as well as a battery of genes involved in several as pects of muscle function. Notable among this group were the growth factor g ene lgf2 and its binding protein Igfbp5. Relevance of this model was sugges ted by verification that three of these genes (IGFBP5, HSIX1, and Slug) wer e also expressed in alveolar rhabdomyosarcoma cell lines. This study utiliz es cDNA microarrays to elucidate the pattern of gene expression induced by an oncogenic transcription factor and demonstrates the profound myogenic pr operties of PAX3-FKHR in NIH 3T3 cells.