The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype
| Autor: | Brian G Van Ness, Paula A. Croonquist |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
Cancer Research
Histone methyltransferase activity Cellular differentiation medicine.medical_treatment Mice Nude macromolecular substances Biology Catalysis Mice Growth factor receptor Gene expression Genetics medicine Animals Humans Enhancer of Zeste Homolog 2 Protein Molecular Biology Cell Proliferation Mice Inbred BALB C Cell growth Interleukin-6 Growth factor EZH2 Polycomb Repressive Complex 2 Cell Differentiation Cell cycle Molecular biology DNA-Binding Proteins Genes ras Phenotype Mutation NIH 3T3 Cells Multiple Myeloma Cell Division Transcription Factors |
| Zdroj: | Oncogene. 24(41) |
| ISSN: | 0950-9232 |
| Popis: | Three distinct proliferative signals for multiple myeloma (MM) cell lines induce enhancer of zeste homolog 2 (ezh 2) transcript expression. EZH 2 is a polycomb group protein that mediates repression of gene transcription at the chromatin level through its methyltransferase activity. Normal bone marrow plasma cells do not express ezh2; however, gene expression is induced and correlates with tumor burden during progression of this disease. We therefore investigated how EZH 2 expression is deregulated in MM cell lines and determined the consequence of this activity on proliferation and transformation. We found that EZH 2 protein expression is induced by interleukin 6 (IL-6) in growth factor-dependent cell lines and is constitutive in IL-6-independent cell lines. Furthermore, EZH 2 expression correlates with proliferation and B-cell terminal differentiation. Significantly, EZH 2 protein inhibition by short interference RNA treatment results in MM cell growth arrest. Conversely, EZH 2 ectopic overexpression induces growth factor independence. We found that the growth factor-independent proliferative phenotype in MM cell lines harboring a mutant N- or K-ras gene requires EZH 2 activity. Finally, this is the first report to demonstrate that EZH 2 has oncogenic activity in vivo, and that cell transformation and tumor formation require histone methyltransferase activity. |
| Databáze: | OpenAIRE |
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