Title |
Comparative expression profiling identifies an in vivo target gene signature with TFAP2B as a mediator of the survival function of PAX3/FKHR
|
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Published in |
Oncogene, May 2007
|
DOI | 10.1038/sj.onc.1210525 |
Pubmed ID | |
Authors |
M Ebauer, M Wachtel, F K Niggli, B W Schäfer |
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. |
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Geographical breakdown
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Unknown | 39 | 95% |
Demographic breakdown
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Researcher | 7 | 17% |
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Student > Master | 4 | 10% |
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Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
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