Polycomb group protein enhancer of zeste 2 is an oncogene that promotes the neoplastic transformation of a benign prostatic epithelial cell line

Breanne D W Karanikolas, Marxa L. Figueiredo, Lily Wu

Research output: Contribution to journalArticle

43 Citations (Scopus)

Abstract

Polycomb group protein enhancer of zeste 2 (EZH2) is a master regulatory protein that plays a critical role in development as part of the polycomb repressive complex 2. Polycomb repressive complex 2 controls numerous cell cycle and regulatory genes through trimethylation of histone 3, which results in chromatin condensation and transcriptional silencing. EZH2 overexpression has been correlated with high incidence of more aggressive, metastatic prostate cancers. Although this correlation means EZH2 could prove valuable as a biomarker in clinical settings, the question remains whether EZH2 is actually responsible for the initiation of these more aggressive tumor types. In this study, EZH2-mediated neoplastic transformation of the normal prostate epithelial cell line benign prostate hyperplasia 1 (BPH1) was confirmed by in vivo tumor growth and in vitro colony formation. Furthermore, EZH2 transformation resulted in increased invasive behavior of BPH1 cells, indicating that EZH2 may be responsible for aggressive behavior in prostate cancers. BPH1 was also transformed with the classic oncogenes myristoylated Akt and activated Ras(V12) to allow phenotype comparisons with the EZH2-transformed cells. This study marks the first demonstration of neoplastic transformation in prostate cells mediated by EZH2 and establishes that EZH2 possesses stronger transforming activity than Akt but weaker activity than activated Ras.

Original languageEnglish (US)
Pages (from-to)1456-1465
Number of pages10
JournalMolecular Cancer Research
Volume7
Issue number9
DOIs
StatePublished - Sep 2009
Externally publishedYes

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Polycomb-Group Proteins
Oncogenes
Prostate
Epithelial Cells
Polycomb Repressive Complex 2
Cell Line
Hyperplasia
Prostatic Neoplasms
cdc Genes
Regulator Genes
Histones
Chromatin
Neoplasms
Biomarkers
Phenotype
Incidence
Growth
Proteins

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Oncology

Cite this

Polycomb group protein enhancer of zeste 2 is an oncogene that promotes the neoplastic transformation of a benign prostatic epithelial cell line. / Karanikolas, Breanne D W; Figueiredo, Marxa L.; Wu, Lily.

In: Molecular Cancer Research, Vol. 7, No. 9, 09.2009, p. 1456-1465.

Research output: Contribution to journalArticle

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