EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer

Adrian P. Bracken, Diego Pasini, Maria Capra, Elena Prosperini, Elena Colli and Kristian Helin ()
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Adrian P. Bracken: European Institute of Oncology
Diego Pasini: European Institute of Oncology
Maria Capra: European Institute of Oncology
Elena Prosperini: European Institute of Oncology
Elena Colli: European Institute of Oncology
Kristian Helin: European Institute of Oncology

Nature, 2003, vol. 22, issue 20, 5323-5335

Abstract: 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.

Keywords: E2F; EED; EZH2; Polycomb; pRB (search for similar items in EconPapers)
Date: 2003
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DOI: 10.1093/emboj/cdg542

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