ZNF423 Is Critically Required for Retinoic Acid-induced Differentiation and Is a Marker of Neuroblastoma Outcome

被引：113

作者：

Huang, Sidong ^{[1
]}

Laoukili, Jamila ^{[4
]}

Epping, Mirjam T. ^{[1
]}

Koster, Jan ^{[4
]}

Holzel, Michael ^{[1
]}

Westerman, Bart A. ^{[2
,3
]}

Nijkamp, Wouter ^{[1
]}

Hata, Akiko ^{[5
]}

Asgharzadeh, Shahab ^{[6
,7
]}

Seeger, Robert C. ^{[6
,7
]}

Versteeg, Rogier ^{[4
]}

Beijersbergen, Roderick L. ^{[1
]}

Bernards, Rene ^{[1
]}

机构：

[1] Netherlands Canc Inst, Ctr Biomed Genet, Div Mol Carcinogenesis, NL-1066 CX Amsterdam, Netherlands

[2] Netherlands Canc Inst, Ctr Biomed Genet, Div Mol Genet, NL-1066 CX Amsterdam, Netherlands

[3] Netherlands Canc Inst, Canc Genom Ctr, NL-1066 CX Amsterdam, Netherlands

[4] Univ Amsterdam, Acad Med Ctr, Dept Human Genet, NL-1100 DE Amsterdam, Netherlands

[5] Tufts Univ, Sch Med, Tufts Med Ctr, Mol Cardiol Res Inst, Boston, MA 02111 USA

[6] Univ So Calif, Childrens Hosp Los Angeles, Saban Res Inst, Los Angeles, CA 90027 USA

[7] Univ So Calif, Childrens Hosp Los Angeles, Dept Pediat, Div Hematol Oncol, Los Angeles, CA 90027 USA

来源：

CANCER CELL | 2009年 / 15卷 / 04期

基金：

美国国家卫生研究院;

关键词：

GENE-EXPRESSION PROFILES; HIGH-RISK NEUROBLASTOMA; HISTONE DEACETYLASE; NUCLEAR RECEPTORS; TRANSCRIPTIONAL ACTIVATION; CEREBELLAR DEVELOPMENT; FINGER PROTEIN; GROWTH ARREST; CO-REPRESSOR; CELL-LINES;

D O I：

10.1016/j.ccr.2009.02.023

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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 RAR alpha/RXR alpha 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.

引用

页码：328 / 340

页数：13

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