Article

The gene for polycomb group protein enhancer of zeste homolog 2 (EZH2) is amplified in late-stage prostate cancer

Cancer Genetics, Institute of Medical Technology, University of Tampere and Tampere University Hospital, Tampere, Finland.
Genes Chromosomes and Cancer (Impact Factor: 4.04). 07/2006; 45(7):639-45. DOI: 10.1002/gcc.20327
Source: PubMed

ABSTRACT

Overexpression of the polycomb group protein enhancer of zeste homologue 2 (EZH2) has been found in several malignancies, including prostate cancer, with an aggressive phenotype. Amplification of the gene has previously been demonstrated in several malignancies, but not in prostate cancer. Our goal was to evaluate the gene copy number and expression alterations of EZH2 in prostate cancer. The copy number of EZH2 in cell lines (LNCaP, DU145, PC-3, 22Rv1), xenografts (n = 10), and clinical tumors (n = 191) was studied with fluorescence in situ hybridization. All cell lines had a gain of EZH2. Eight of the ten xenografts showed an increased copy number of the gene, including one case of high-level amplification (>or=5 copies of the gene and EZH2/centromere ratio >or=2). 34/125 (27%) of untreated prostate carcinomas showed increased copy number, but only one case of low-level amplification (>or=5 copies of the gene and EZH2/centromere ratio <2), whereas half (25/46) of the hormone-refractory carcinomas showed increased copy number, including seven cases of low-level amplification and three cases of high-level amplification (P < 0.0001). Expression of EZH2 was significantly (P = 0.0009) higher in hormone-refractory prostate cancer compared with that in benign prostatic hyperplasia or untreated cancer, according to quantitative real-time RT-PCR assay. Also, the expression of EZH2 protein was found to be higher in hormone-refractory tumors than in hormone-naïve tumors by immunohistochemistry. The EZH2 gene amplification was significantly (P < 0.05) associated with increased EZH2 protein expression. The data show that amplification of the EZH2 gene is rare in early prostate cancer, whereas a fraction of late-stage tumors contains the gene amplification leading to the overexpression of the gene, thus indicating the importance of EZH2 in the progression of prostate cancer.

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Available from: Outi R Saramäki, Jan 19, 2015
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    • "PRC2 consists of several components, among them EED and SUZ12 promote PRC2 assembly and contribute to the H3K27 methyltransferase activity of EZH2 (O'Meara &amp; Simon 2012). EZH2 is highly expressed in many solid tumors, it is considered to be an oncogene and amplification of EZH2 has been observed in several cancers (Bracken et al. 2003, Saramaki et al. 2006). In lymphoma, heterozygous missense mutations at amino acid Y641 caused higher catalytic efficiency. "
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    • "Microarray studies have linked overexpression of EZH2 to PCa (Varambally et al., 2002). More than half of the hormone-refractory PCa possess increased copies of EZH2 gene, which correlates with high expression levels of EZH2 protein, whereas its amplification and overexpression is rare in early stage PCa, highlighting its potential function in PCa progression (Saramäki et al., 2006). "
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    • "The enhancer of zeste homolog 2 (EZH2, also called histone lysine methyltransferase) is located at chromosome 7q35 and encodes a member of the Polycomb group proteins [7], which regulate gene expression via epigenetic modification of chromatin structure including inducing histone acetylation and methylation [7,8]. Previous studies showed that EZH2 is overexpressed in a broad range of tumors [9,10]. "
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