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Publication : Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer.

First Author  Yu J Year  2007
Journal  Cancer Cell Volume  12
Issue  5 Pages  419-31
PubMed ID  17996646 Mgi Jnum  J:127322
Mgi Id  MGI:3763571 Doi  10.1016/j.ccr.2007.10.016
Citation  Yu J, et al. (2007) Integrative genomics analysis reveals silencing of beta-adrenergic signaling by polycomb in prostate cancer. Cancer Cell 12(5):419-31
abstractText  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.
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