Systematic name M12661
Brief description Genes commonly down-regulated in SK-N-BE cells (neuroblastoma) after RNAi knockdown of CCND1 and CDK4 [GeneID=595;1019].
Full description or abstract Genomic aberrations of Cyclin D1 (CCND1), CDK4, and CDK6 in neuroblastoma indicate that dysregulation of the G(1) entry checkpoint is an important cell cycle aberration in this pediatric tumor. Here, we report that analysis of Affymetrix expression data of primary neuroblastic tumors shows an extensive overexpression of Cyclin D1, which correlates with histologic subgroups. Immunohistochemical analysis showed overexpression of Cyclin D1 in neuroblasts and low Cyclin D1 expression in all cell types in ganglioneuroma. This suggests an involvement of G(1)-regulating genes in neuronal differentiation processes which we further evaluated using RNA interference against Cyclin D1 and its kinase partners CDK4 and CDK6 in several neuroblastoma cell lines. The Cyclin D1 and CDK4 knockdown resulted in pRb pathway inhibition as shown by an almost complete disappearance of CDK4/CDK6-specific pRb phosphorylation, reduction of E2F transcriptional activity, and a decrease of Cyclin A protein levels. Phenotype analysis showed a significant reduction in cell proliferation, a G(1)-specific cell cycle arrest, and, moreover, an extensive neuronal differentiation. Affymetrix microarray profiling of small interfering RNA-treated cells revealed a shift in expression profile toward a neuronal phenotype. Several new potential downstream players are identified. We conclude that neuroblastoma functionally depend on overexpression of G(1)-regulating genes to maintain their undifferentiated phenotype.
Collection C2: Curated
      CGP: Chemical and Genetic Perturbations
Source publication Pubmed 18413728   Authors: Molenaar JJ,Ebus ME,Koster J,van Sluis P,van Noesel CJ,Versteeg R,Caron HN
Exact source Table 2B
Related gene sets (show 1 additional gene sets from the source publication)

(show 3 gene sets from the same authors)
External links
Filtered by similarity ?
Source species Homo sapiens
Contributed by Jessica Robertson (MSigDB Team)
Source platform or
identifier namespace
Dataset references (show 1 datasets)
Download gene set format: grp | gmt | xml | json | TSV metadata
Compute overlaps ? (show collections to investigate for overlap with this gene set)
Compendia expression profiles ? NG-CHM interactive heatmaps
(Please note that clustering takes a few seconds)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)

Legacy heatmaps (PNG)
GTEx compendium
Human tissue compendium (Novartis)
Global Cancer Map (Broad Institute)
NCI-60 cell lines (National Cancer Institute)
Advanced query Further investigate these 59 genes
Gene families ? Categorize these 59 genes by gene family
Show members (show 59 source identifiers mapped to 59 genes)
Version history 3.0: First introduced

See MSigDB license terms here. Please note that certain gene sets have special access terms.