Elucidation of the Downstream Targets of the PAX3-FKHR Fusion Oncogene Found in Aveolar Rhabdomyosarcoma Using cDNA Microarrays

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Abstract 863 Hematology-Oncology II Poster Symposium, Sunday, 5/2

cDNA microarrays allows large scale analysis of the effects of oncogenic transcription factors on gene expression. In the aggressive muscle cancer, alveolar rhabdomyosarcoma (ARMS), the majority (60%) of tumors contain a characteristic translocation the t(2;13)(q35;q14). This results in the chimeric PAX3-FKHR gene in which the DNA binding domain of PAX3 is linked to the trans-activation domain of FKHR. Using retroviral transduction we have introduced both PAX3 and PAX3-FKHR into NIH3T3 cells and utilized a mouse cDNA microarray containing 2200 elements to investigate their effects on gene expression. Introduction of PAX3-FKHR resulted in increased expression of several genes including the myogenic transcription factor myogenin, as well as other muscle specific genes. In complete contrast PAX3 failed to induce these genes and indeed repressed several genes, some of which were also down-regulated by PAX3-FKHR. This study demonstrates the potential of cDNA microarrays to elucidate the pathways of malignant transformation by oncogenic transcription factors.

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