Systematic name M4364
Brief description Genes down-regulated in K562 (chronic myelogenous leukemia, CML) cells engineered to stably express RIZ1 [GeneID=7799].
Full description or abstract RIZ1 is a histone methyltransferase whose expression and activity are reduced in many cancers. In chronic myelogenous leukemia (CML), blastic transformation is associated with loss of heterozygosity in the region where RIZ1 is located and with decreased RIZ1 expression. Forced RIZ1 expression in model CML blast crisis (BC) cell lines decreases proliferation, increases apoptosis and enhances differentiation. We characterized molecular mechanisms that may contribute to potential CML tumor suppressor properties of RIZ1. Several RIZ1-regulated genes involved in insulin-like growth factor-1 (IGF-1) signaling were identified using cDNA microarrays. RIZ1 was shown to associate with promoter regions of IGF-1 and to increase histone H3 lysine 9 methylation using chromatin immunoprecipitation assays. IGF-1-blocking antibody was used to demonstrate the importance of autocrine IGF-1 signaling in CML-BC cell line viability. Forced RIZ1 expression in CML-BC cell lines decreases IGF-1 receptor activation and activation of downstream signaling components extracellular signal-regulated kinase 1/2 and AKT. These results highlight the therapeutic potential of inhibiting IGF-1 pathway in the acute phase of CML.
Collection C2: curated gene sets
      CGP: chemical and genetic perturbations
Source publication Pubmed 16953217   Authors: Pastural E,Takahashi N,Dong WF,Bainbridge M,Hull A,Pearson D,Huang S,Lowsky R,DeCoteau JF,Geyer CR
Exact source Table 1: Downregulated
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Organism Homo sapiens
Contributed by Aravind Subramanian (MSigDB Team)
Source platform HUMAN_GENE_SYMBOL
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