TY - JOUR
T1 - ZNF423 Is Critically Required for Retinoic Acid-Induced Differentiation and Is a Marker of Neuroblastoma Outcome
AU - Huang, Sidong
AU - Laoukili, Jamila
AU - Epping, Mirjam T.
AU - Koster, Jan
AU - Hölzel, Michael
AU - Westerman, Bart A.
AU - Nijkamp, Wouter
AU - Hata, Akiko
AU - Asgharzadeh, Shahab
AU - Seeger, Robert C.
AU - Versteeg, Rogier
AU - Beijersbergen, Roderick L.
AU - Bernards, René
PY - 2009/4/7
Y1 - 2009/4/7
N2 - 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 RARα/RXRα 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.
AB - 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 RARα/RXRα 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.
KW - CELLCYCLE
UR - http://www.scopus.com/inward/record.url?scp=63449100807&partnerID=8YFLogxK
U2 - https://doi.org/10.1016/j.ccr.2009.02.023
DO - https://doi.org/10.1016/j.ccr.2009.02.023
M3 - Article
C2 - 19345331
SN - 1535-6108
VL - 15
SP - 328
EP - 340
JO - Cancer cell
JF - Cancer cell
IS - 4
ER -