RIZ1 repression is associated with insulin-like growth factor-1 signaling activation in chronic myeloid leukemia cell lines
| Autor: | Robert Lowsky, C R Geyer, Andrea R. Hull, Elodie Pastural, Matthew Bainbridge, John F. DeCoteau, Naoto Takahashi, Shi Huang, Derek Pearson, Wei-Feng Dong |
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| Rok vydání: | 2006 |
| Předmět: |
Cancer Research
Biology Methylation Histones Histone H3 Leukemia Myelogenous Chronic BCR-ABL Positive hemic and lymphatic diseases Genetics medicine Humans Insulin-Like Growth Factor I Promoter Regions Genetic Autocrine signalling Molecular Biology Protein kinase B Oligonucleotide Array Sequence Analysis Lysine Nuclear Proteins Histone-Lysine N-Methyltransferase medicine.disease DNA-Binding Proteins Gene Expression Regulation Histone methyltransferase Cancer research Signal transduction K562 Cells Chromatin immunoprecipitation Signal Transduction Transcription Factors Chronic myelogenous leukemia K562 cells |
| Zdroj: | Oncogene. 26:1586-1594 |
| ISSN: | 1476-5594 0950-9232 |
| DOI: | 10.1038/sj.onc.1209959 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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