Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer

Academic Article

Abstract

  • The Polycomb group (PcG) protein EZH2 possesses oncogenic properties for which the underlying mechanism is unclear. We integrated in vitro cell line, in vivo tumor profiling, and genome-wide location data to nominate key targets of EZH2. One of the candidates identified was ADRB2 (Adrenergic Receptor, Beta-2), a critical mediator of β-adrenergic signaling. EZH2 is recruited to the ADRB2 promoter and represses ADRB2 expression. ADRB2 inhibition confers cell invasion and transforms benign prostate epithelial cells, whereas ADRB2 overexpression counteracts EZH2-mediated oncogenesis. ADRB2 is underexpressed in metastatic prostate cancer, and clinically localized tumors that express lower levels of ADRB2 exhibit a poor prognosis. Taken together, we demonstrate the power of integrating multiple diverse genomic data to decipher targets of disease-related genes. © 2007 Elsevier Inc. All rights reserved.
  • Published In

  • Cancer Cell  Journal
  • Digital Object Identifier (doi)

    Author List

  • Yu J; Cao Q; Mehra R; Laxman B; Yu J; Tomlins SA; Creighton CJ; Dhanasekaran SM; Shen R; Chen G
  • Start Page

  • 419
  • End Page

  • 431
  • Volume

  • 12
  • Issue

  • 5