title: EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.
abstract: Recent experiments have demonstrated that the Polycomb group (PcG) gene EZH2 is highly expressed in metastatic prostate cancer and in lymphomas. EZH2 is a component of the PRC2 histone methyltransferase complex, which also contains EED and SUZ12 and is required for the silencing of HOX gene expression during embryonic development. Here we demonstrate that both EZH2 and EED are essential for the proliferation of both transformed and non-transformed human cells. In addition, the pRB-E2F pathway tightly regulates their expression and, consistent with this, we find that EZH2 is highly expressed in a large set of human tumors. These results raise the question whether EZH2 is a marker of proliferation or if it is actually contributing to tumor formation. Significantly, we propose that EZH2 is a bona fide oncogene, since we find that ectopic expression of EZH2 is capable of providing a proliferative advantage to primary cells and, in addition, its gene locus is specifically amplified in several primary tumors.
authors.affiliation: European Institute of Oncology, Department of Experimental Oncology, Via Ripamonti 435, 20141 Milan, Italy.
authors.forename: Adrian P
authors.initials: AP
authors.lastname: Bracken
authors.forename: Diego
authors.initials: D
authors.lastname: Pasini
authors.forename: Maria
authors.initials: M
authors.lastname: Capra
authors.forename: Elena
authors.initials: E
authors.lastname: Prosperini
authors.forename: Elena
authors.initials: E
authors.lastname: Colli
authors.forename: Kristian
authors.initials: K
authors.lastname: Helin
mesh_terms: D000818:Animals; D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics; D002455:Cell Division; D002460:Cell Line; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D000071221:Enhancer of Zeste Homolog 2 Protein; D005784:Gene Amplification; D005819:Genetic Markers; D006801:Humans; D007700:Kinetics; D008223:Lymphoma / Q000235:genetics; D008297:Male; D009857:Oncogenes; D063151:Polycomb Repressive Complex 2; D011401:Promoter Regions, Genetic / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics; D011506:Proteins / Q000235:genetics*; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D016160:Retinoblastoma Protein / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism*; D015533:Transcriptional Activation; D014162:Transfection
chemical_list: D018797:Cell Cycle Proteins; D017931:DNA Primers; D004268:DNA-Binding Proteins; D050684:E2F Transcription Factors; D005819:Genetic Markers; D011506:Proteins; D011994:Recombinant Proteins; D016160:Retinoblastoma Protein; D014157:Transcription Factors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2