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

TY - JOUR

T1 - EZH2 is downstream of the pRB-E2F pathway, essential for proliferation and amplified in cancer.

AU - Bracken, Adrian P

AU - Pasini, Diego

AU - Capra, Maria

AU - Prosperini, Elena

AU - Colli, Elena

AU - Helin, Kristian

N1 - Keywords: Animals; Base Sequence; Cell Cycle Proteins; Cell Division; Cell Line; DNA Primers; DNA-Binding Proteins; E2F Transcription Factors; Gene Amplification; Genetic Markers; Humans; Kinetics; Lymphoma; Male; Oncogenes; Promoter Regions (Genetics); Prostatic Neoplasms; Proteins; Rats; Recombinant Proteins; Retinoblastoma Protein; Trans-Activation (Genetics); Transcription Factors; Transfection

PY - 2003

Y1 - 2003

N2 - 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.

AB - 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.

U2 - 10.1093/emboj/cdg542

DO - 10.1093/emboj/cdg542

M3 - Journal article

C2 - 14532106

SN - 0261-4189

VL - 22

SP - 5323

EP - 5335

JO - E M B O Journal

JF - E M B O Journal

IS - 20

ER -