CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression

Z. Liu, X. Yang, Z. Li, C. McMahon, C. Sizer, L. Barenboim-Stapleton, V. Bliskovsky, B. Mock, T. Ried, W. B. London, J. Maris, J. Khan, C. J. Thiele

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P0.0002) and decreased survival probability (P0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.

Original languageEnglish (US)
Pages (from-to)1174-1183
Number of pages10
JournalCell Death and Differentiation
Volume18
Issue number7
DOIs
StatePublished - Jul 2011
Externally publishedYes

Fingerprint

Tumor Suppressor Genes
Neuroblastoma
Gene Expression
Growth
Neoplasms
Loss of Heterozygosity
Carcinogenesis
Cell Growth Processes
Chromosomes
Zinc Fingers
Sympathetic Nervous System
Retinoids
Gene Silencing
Epigenomics
Cell Adhesion
Drosophila
Real-Time Polymerase Chain Reaction
Cell Differentiation
Transcription Factors
Phenotype

Keywords

  • CASZ1
  • chromosome 1p
  • developmental gene
  • neuroblastoma
  • transcription factor
  • tumor suppressor

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Liu, Z., Yang, X., Li, Z., McMahon, C., Sizer, C., Barenboim-Stapleton, L., ... Thiele, C. J. (2011). CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. Cell Death and Differentiation, 18(7), 1174-1183. https://doi.org/10.1038/cdd.2010.187

CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. / Liu, Z.; Yang, X.; Li, Z.; McMahon, C.; Sizer, C.; Barenboim-Stapleton, L.; Bliskovsky, V.; Mock, B.; Ried, T.; London, W. B.; Maris, J.; Khan, J.; Thiele, C. J.

In: Cell Death and Differentiation, Vol. 18, No. 7, 07.2011, p. 1174-1183.

Research output: Contribution to journalArticle

Liu, Z, Yang, X, Li, Z, McMahon, C, Sizer, C, Barenboim-Stapleton, L, Bliskovsky, V, Mock, B, Ried, T, London, WB, Maris, J, Khan, J & Thiele, CJ 2011, 'CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression', Cell Death and Differentiation, vol. 18, no. 7, pp. 1174-1183. https://doi.org/10.1038/cdd.2010.187
Liu, Z. ; Yang, X. ; Li, Z. ; McMahon, C. ; Sizer, C. ; Barenboim-Stapleton, L. ; Bliskovsky, V. ; Mock, B. ; Ried, T. ; London, W. B. ; Maris, J. ; Khan, J. ; Thiele, C. J. / CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression. In: Cell Death and Differentiation. 2011 ; Vol. 18, No. 7. pp. 1174-1183.
@article{6cbe0dd35e3a4919b73295c054ce4078,
title = "CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression",
abstract = "Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P0.0002) and decreased survival probability (P0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.",
keywords = "CASZ1, chromosome 1p, developmental gene, neuroblastoma, transcription factor, tumor suppressor",
author = "Z. Liu and X. Yang and Z. Li and C. McMahon and C. Sizer and L. Barenboim-Stapleton and V. Bliskovsky and B. Mock and T. Ried and London, {W. B.} and J. Maris and J. Khan and Thiele, {C. J.}",
year = "2011",
month = "7",
doi = "10.1038/cdd.2010.187",
language = "English (US)",
volume = "18",
pages = "1174--1183",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - CASZ1, a candidate tumor-suppressor gene, suppresses neuroblastoma tumor growth through reprogramming gene expression

AU - Liu, Z.

AU - Yang, X.

AU - Li, Z.

AU - McMahon, C.

AU - Sizer, C.

AU - Barenboim-Stapleton, L.

AU - Bliskovsky, V.

AU - Mock, B.

AU - Ried, T.

AU - London, W. B.

AU - Maris, J.

AU - Khan, J.

AU - Thiele, C. J.

PY - 2011/7

Y1 - 2011/7

N2 - Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P0.0002) and decreased survival probability (P0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.

AB - Neuroblastoma (NB) is a common childhood malignant tumor of the neural crest-derived sympathetic nervous system. In NB the frequent loss of heterozygosity (LOH) on chromosome 1p raises the possibility that this region contains tumor-suppressor genes whose inactivation contributes to tumorigenesis. The human homolog of the Drosophila neural fate determination gene CASZ1, a zinc-finger transcription factor, maps to chromosome 1p36.22, a region implicated in NB tumorigenesis. Quantitative real-time PCR analysis showed that low-CASZ1 expression is significantly correlated with increased age (18 months), Children's Oncology Group high-risk classification, 1p LOH and MYCN amplification (all P0.0002) and decreased survival probability (P0.0009). CASZ1 was more highly expressed in NB with a differentiated histopathology (P0.0001). Retinoids and epigenetic modification agents associated with regulation of differentiation induced CASZ1 expression. Expression profiling analysis revealed that CASZ1 regulates the expression of genes involved in regulation of cell growth and developmental processes. Specific restoration of CASZ1 in NB cells induced cell differentiation, enhanced cell adhesion, inhibited migration and suppressed tumorigenicity. These data are consistent with CASZ1 being a critical modulator of neural cell development, and that somatically acquired disruption of normal CASZ1 expression contributes to the malignant phenotype of human NB.

KW - CASZ1

KW - chromosome 1p

KW - developmental gene

KW - neuroblastoma

KW - transcription factor

KW - tumor suppressor

UR - http://www.scopus.com/inward/record.url?scp=79958804414&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=79958804414&partnerID=8YFLogxK

U2 - 10.1038/cdd.2010.187

DO - 10.1038/cdd.2010.187

M3 - Article

VL - 18

SP - 1174

EP - 1183

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 7

ER -