Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR

M Ebauer, M Wachtel, FK Niggli, BW Schäfer - Oncogene, 2007 - nature.com
M Ebauer, M Wachtel, FK Niggli, BW Schäfer
Oncogene, 2007nature.com
Abstract The chromosomal translocation t (2; 13), characteristic for the aggressive childhood
cancer alveolar rhabdomyosarcoma (aRMS), generates the chimeric transcription factor
PAX3/FKHR with a well known oncogenic role. However, the molecular mechanisms
mediating essential pathophysiological functions remain poorly defined. Here, we used
comparative expression profiling of PAX3/FKHR silencing in vitro and PAX3/FKHR-specific
gene signatures in vivo to identify physiologically important target genes. Hereby, 51 …
Abstract
The chromosomal translocation t (2; 13), characteristic for the aggressive childhood cancer alveolar rhabdomyosarcoma (aRMS), generates the chimeric transcription factor PAX3/FKHR with a well known oncogenic role. However, the molecular mechanisms mediating essential pathophysiological functions remain poorly defined. Here, we used comparative expression profiling of PAX3/FKHR silencing in vitro and PAX3/FKHR-specific gene signatures in vivo to identify physiologically important target genes. Hereby, 51 activated genes, both novel and known, were identified. We also found repression of skeletal muscle-specific genes suggesting that PAX3/FKHR blocks further differentiation of aRMS cells. Importantly, TFAP2B was validated as direct target gene mediating the anti-apoptotic function of PAX3/FKHR. Hence, we developed a pathophysiologically relevant transcriptional profile of PAX3/FKHR and identified a critical target gene for aRMS development.
nature.com