Integrative genomics analysis reveals silencing of β-adrenergic signaling by polycomb in prostate cancer. Yu J, Cao Q, Mehra R, Laxman B, Yu J, Tomlins SA, Creighton CJ, Dhanasekaran SM, Shen R, Chen G, Morris DS, Marquez VE, Shah RB, Ghosh D, Varambally S, Chinnaiyan AM, Department of Pathology, Michigan Center for Translational Pathology, University of Michigan Medical School, Ann Arbor, MI

Research output: Contribution to journalShort surveypeer-review

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, β-2), a critical mediator of beta-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.

Original languageEnglish (US)
Pages (from-to)686-687
Number of pages2
JournalUrologic Oncology: Seminars and Original Investigations
Volume26
Issue number6
DOIs
StatePublished - Nov 2008

Bibliographical note

Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.

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