@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.}",
note = "Funding Information: Acknowledgements. We would like to thank the Children s Oncology Group (COG) Neuroblastoma Biology Group Committee for providing us with total RNA from neuroblastoma tumors from patients prior to chemotherapy. We thank Dr. Cris Q. Doe of Howard Hughes Medical Institute, University of Oregon for the critical reading of the manuscript. We would like to thank Drs. Chris Redfern, and Quentin Campbell Hewson of the Northern Institute for Cancer Research, Newcastle University, UK for providing us with the SY5Ytet (SY5Ytet12) cell line. The NGFR promoter – pGL3 basic vectors were generously provided by Philip Barker (Centre for Neuronal Survival, Montreal Neurological Institute, McGill University, Canada). The control vector pDest-30 with an out-of-frame CAT gene with no start codon was generously provided by Dominic Esposito (Protein Expression Laboratory, SAIC-Frederick, Inc.). We thank the CCR{\textquoteright}s Office of Science and Technology Partnerships, Drs. Shoshana Segal and David Goldstein for their coordination of the strategic partnerships that were key for microarray services. The authors thank Ms. Lauren Marks for her excellent support of the Cell and Molecular Biology Section, POB, CCR, NCI. This research was supported by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The study of NB tumor samples was done through the COG NB Biology Project 2004-01, with COG funding from grant number U10 CA98413.",
year = "2011",
month = jul,
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",
}