The polycomb group protein EZH2 is involved in progression of prostate cancer.
Prostate cancer is a leading cause of cancer-related death in males and is second only to lung cancer. Although effective surgical and radiation treatments exist for clinically localized prostate cancer, metastatic prostate cancer remains essentially incurable. Here we show, through gene expression profiling, that the polycomb group protein enhancer of zeste homolog 2 (EZH2) is overexpressed in hormone-refractory, metastatic prostate cancer. Small interfering RNA (siRNA) duplexes targeted against EZH2 reduce the amounts of EZH2 protein present in prostate cells and also inhibit cell proliferation in vitro. Ectopic expression of EZH2 in prostate cells induces transcriptional repression of a specific cohort of genes. Gene silencing mediated by EZH2 requires the SET domain and is attenuated by inhibiting histone deacetylase activity. Amounts of both EZH2 messenger RNA and EZH2 protein are increased in metastatic prostate cancer; in addition, clinically localized prostate cancers that express higher concentrations of EZH2 show a poorer prognosis. Thus, dysregulated expression of EZH2 may be involved in the progression of prostate cancer, as well as being a marker that distinguishes indolent prostate cancer from those at risk of lethal progression.
Varambally
Sooryanarayana
S
Department of Pathology, University of Michigan Medical School, Ann Arbor, Michigan 48109, USA.
Dhanasekaran
Saravana M
SM
Zhou
Ming
M
Barrette
Terrence R
TR
Kumar-Sinha
Chandan
C
Sanda
Martin G
MG
Ghosh
Debashis
D
Pienta
Kenneth J
KJ
Sewalt
Richard G A B
RG
Otte
Arie P
AP
Rubin
Mark A
MA
Chinnaiyan
Arul M
AM
D014408:Biomarkers, Tumor; D018450:Disease Progression; D029721:Drosophila Proteins / Q000235:genetics / Q000502:physiology*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D016147:Genes, Tumor Suppressor; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D063151:Polycomb Repressive Complex 2; D011237:Predictive Value of Tests; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*; D014162:Transfection; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D029721:Drosophila Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D012097:Repressor Proteins; C083329:E(z) protein, Drosophila; D063151:Polycomb Repressive Complex 2