| Literature DB >> 17996646 |
Jindan Yu1, Qi Cao, Rohit Mehra, Bharathi Laxman, Jianjun Yu, Scott A Tomlins, Chad J Creighton, Saravana M Dhanasekaran, Ronglai Shen, Guoan Chen, David S Morris, Victor E Marquez, Rajal B Shah, Debashis Ghosh, Sooryanarayana Varambally, Arul M Chinnaiyan.
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 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.Entities:
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Year: 2007 PMID： 17996646 DOI： 10.1016/j.ccr.2007.10.016
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743