Klin Padiatr 2013; 225 - A27
DOI: 10.1055/s-0033-1343644

The transcription factor activating protein 2 beta (TFAP2B) mediates neuronal differentiation in neuroblastoma cells

F Sherkheli 1, 2, 3, S Ackermann 1, 2, F Roels 1, 2, H Kocak 1, 2, R Volland 1, R Thomas 4, M Fischer 1, 2
  • 1Children's Hospital, Dept. of Pediatric Oncology and Hematology, University of Cologne
  • 2Center for Molecular Medicine Cologne (CMMC), University of Cologne
  • 3Cologne Center for Genomics (CCG), University of Cologne
  • 4Department of Translational Genomics, University of Cologne, Germany

We here aimed to investigate the role of the transcription factor activating protein 2 beta (TFAP2B) in neuroblastoma pathogenesis. TFAP2 is a family of transcription factors that play a crucial role in embryonic differentiation and development. Oligonucleotide-microarray analysis of 649 neuroblastoma specimens demonstrated that TFAP2B downregulation is associated with unfavourable prognostic markers such as disseminated stage 4, age > 18 months, MYCN amplification, unfavourable gene expression-based classification and adverse patient outcome.

Tetracycline inducible re-expression of TFAP2B in neuroblastoma cells significantly impaired proliferation and led to arrest in the G1-phase of the cell cycle in IMR-32 and SH-EP cells. Neuronal differentiation and senescence was observed in IMR-32 and SH-EP cells, respectively, after TFAP2B induction. In addition, knockdown of TFAP2B by lentiviral transduction of shRNA abrogated retinoic acid induced neuronal differentiation of SH-SY5Y and SK-N-Be(2)-C cells. Taken together, our results point towards a role of TFAP2B in neuronal differentiation of neuroblastoma.