The polycomb group protein enhancer of zeste homolog 2 (EZH 2) is an oncogene that influences myeloma cell growth and the mutant ras phenotype.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8711562 Publication Model: Print Cited Medium: Print ISSN: 0950-9232 (Print) Linking ISSN: 09509232 NLM ISO Abbreviation: Oncogene Subsets: MEDLINE

Publication: <2002->: Basingstoke : Nature Publishing Group
Original Publication: Basingstoke, Hampshire, UK : Scientific & Medical Division, MacMillan Press, c1987-

Genes, ras* ; Mutation*; Cell Division/*genetics ; DNA-Binding Proteins/*genetics ; Multiple Myeloma/*genetics ; Transcription Factors/*genetics; Animals ; Catalysis ; Cell Differentiation ; Cell Proliferation ; DNA-Binding Proteins/metabolism ; Enhancer of Zeste Homolog 2 Protein ; Humans ; Interleukin-6/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Multiple Myeloma/pathology ; NIH 3T3 Cells ; Phenotype ; Polycomb Repressive Complex 2 ; Transcription Factors/metabolism

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.
(Oncogene (2005) 24, 6269-6280.)

CA09138 United States CA NCI NIH HHS; CA62242 United States CA NCI NIH HHS

0 (DNA-Binding Proteins)
0 (Interleukin-6)
0 (Transcription Factors)
EC 2.1.1.43 (EZH2 protein, human)
EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein)
EC 2.1.1.43 (Polycomb Repressive Complex 2)

Date Created: 20050712 Date Completed: 20051121 Latest Revision: 20161124

20231215

10.1038/sj.onc.1208771

16007202