ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome.
 

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04-07-09 10:10 AM
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ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome.
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ZNF423 is critically required for retinoic acid-induced differentiation and is a marker of neuroblastoma outcome.

Cancer Cell. 2009 Apr 7;15(4):328-40

Authors: Huang S, Laoukili J, Epping MT, Koster J, Hölzel M, Westerman BA, Nijkamp W, Hata A, Asgharzadeh S, Seeger RC, Versteeg R, Beijersbergen RL, Bernards R

Retinoids play key roles in differentiation, growth arrest, and apoptosis and are increasingly being used in the clinic for the treatment of a variety of cancers, including neuroblastoma. Here, using a large-scale RNA interference-based genetic screen, we identify ZNF423 (also known as Ebfaz, OAZ, or Zfp423) as a component critically required for retinoic acid (RA)-induced differentiation. ZNF423 associates with the RARalpha/RXRalpha nuclear receptor complex and is essential for transactivation in response to retinoids. Downregulation of ZNF423 expression by RNA interference in neuroblastoma cells results in a growth advantage and resistance to RA-induced differentiation, whereas overexpression of ZNF423 leads to growth inhibition and enhanced differentiation. Finally, we show that low ZNF423 expression is associated with poor disease outcome in neuroblastoma patients.

PMID: 19345331 [PubMed - in process]