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

Oncogene. 2007 Nov 8;26(51):7267-81. doi: 10.1038/sj.onc.1210525. Epub 2007 May 21.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Survival / physiology*
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors / physiology*
  • Gene Expression Profiling*
  • Humans
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / physiology*
  • Transcription Factor AP-2 / physiology*


  • FOXO1 protein, human
  • Forkhead Box Protein O1
  • Forkhead Transcription Factors
  • PAX3 Transcription Factor
  • PAX3 protein, human
  • Paired Box Transcription Factors
  • TFAP2B protein, human
  • Transcription Factor AP-2