The polycomb proteins BMI-1, EZH2, and SIRT1 are characteristic components of 
the PRC1, PRC2, and PRC4 repressor complexes, respectively, that modify 
chromatin. Moreover, EZH2 may influence DNA methylation by direct interaction 
with DNA methyltransferases. EZH2 expression increases during prostate cancer 
progression, whereas BMI-1 and SIRT1 are not well investigated. Like EZH2 
expression, DNA methylation alterations escalate in higher stage prostate 
cancers, raising the question whether these epigenetic changes are related. 
Expression of EZH2, BMI-1, SIRT1, and the DNA methyltransferases DNMT1 and 
DNMT3B measured by qRT-PCR in 47 primary prostate cancers was compared to APC, 
ASC, GSTP1, RARB2, and RASSF1A hypermethylation and LINE-1 hypomethylation. 
SIRT1 and DNMT3B were overexpressed in cancerous over benign tissues, whereas 
BMI-1 was rather downregulated and DNMT1 significantly diminished. Nevertheless, 
cancers with higher DNMT1 and BMI-1 expression had worse clinical 
characteristics, as did those with elevated EZH2. In particular, above median 
DNMT1 expression predicted a worse prognosis. EZH2 and SIRT1 overexpression were 
well correlated with increased MKI67. Immunohistochemistry confirmed limited 
EZH2 and heterogeneous DNMT3B overexpression and explained the decrease in BMI-1 
by pronounced heterogeneity among tumor cells. EZH2 overexpression, specifically 
among all factors investigated, was associated with more frequent 
hypermethylation, in particular of GSTP1 and RARB2, and also with LINE-1 
hypomethylation. Our data reveal complex changes in the composition of polycomb 
repressor complexes in prostate cancer. Heterogeneously expressed BMI-1 and 
slightly increased EZH2 may characterize less malignant cancers, whereas more 
aggressive cases express both at higher levels. SIRT1 appears to be generally 
increased in prostate cancers. Intriguingly, our data suggest a direct influence 
of increased EZH2 on altered DNA methylation patterns in prostate cancer.