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CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells

Item Type:Article
Title:CAMTA1, a 1p36 tumor suppressor candidate, inhibits growth and activates differentiation programs in neuroblastoma cells
Creators Name:Henrich, K.O. and Bauer, T. and Schulte, J. and Ehemann, V. and Deubzer, H. and Gogolin, S. and Muth, D. and Fischer, M. and Benner, A. and König, R. and Schwab, M. and Westermann, F.
Abstract:A distal portion of human chromosome 1p is often deleted in neuroblastomas and other cancers and it is generally assumed that this region harbors one or more tumor suppressor genes. In neuroblastoma, a 261 kb region at 1p36.3 that encompasses the smallest region of consistent deletion pinpoints the locus for calmodulin binding transcription activator 1 (CAMTA1). Low CAMTA1 expression is an independent predictor of poor outcome in multivariate survival analysis, but its potential functionality in neuroblastoma has not been explored. In this study, we used inducible cell models to analyze the impact of CAMTA1 on neuroblastoma biology. In neuroblastoma cells that expressed little endogenous CAMTA1, its ectopic expression slowed cell proliferation, increasing the relative proportion of cells in G(1)/G(0) phases of the cell cycle, inhibited anchorage-independent colony formation, and suppressed the growth of tumor xenografts. CAMTA1 also induced neurite-like processes and markers of neuronal differentiation in neuroblastoma cells. Further, retinoic acid and other differentiation- inducing stimuli upregulated CAMTA1 expression in neuroblastoma cells. Transciptome analysis revealed 683 genes regulated on CAMTA1 induction and gene ontology analysis identified genes consistent with CAMTA1-induced phenotypes, with a significant enrichment for genes involved in neuronal function and differentiation. Our findings define properties of CAMTA1 in growth suppression and neuronal differentiation that support its assignment as a 1p36 tumor suppressor gene in neuroblastoma.
Keywords:Amino Acid Sequence, Calcium-Binding Proteins, Cell Differentiation, Cell Growth Processes, Human Pair 1 Chromosomes, Molecular Sequence Data, Neuroblastoma, Nude Mice, Trans-Activators, Tumor Cell Line, Tumor Suppressor Genes, Up-Regulation, Animals, Mice
Source:Cancer Research
ISSN:0008-5472
Publisher:American Association for Cancer Research (U.S.A.)
Volume:71
Number:8
Page Range:3142-3151
Date:15 April 2011
Official Publication:https://doi.org/10.1158/0008-5472.CAN-10-3014
PubMed:View item in PubMed

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