@article{7d6f03e23d014edb927f65c9e4d706a7,
title = "Integrative Genomics Analysis Reveals Silencing of β-Adrenergic Signaling by Polycomb in Prostate Cancer",
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.",
keywords = "CELLCYCLE, SYSBIO",
author = "Jindan Yu and Qi Cao and Rohit Mehra and Bharathi Laxman and Jianjun Yu and Tomlins, {Scott A.} and Creighton, {Chad J.} and Dhanasekaran, {Saravana M.} and Ronglai Shen and Guoan Chen and Morris, {David S.} and Marquez, {Victor E.} and Shah, {Rajal B.} and Debashis Ghosh and Sooryanarayana Varambally and Chinnaiyan, {Arul M.}",
note = "Funding Information: The authors would like to thank Xiaoju Wang for helpful discussions, Wenjun Zhou for technical assistance, and the staff of the Microscopy and Image Analyses laboratory at the University of Michigan for their help in cell imaging. A.M.C. is supported by a Burroughs Welcome Foundation Award in Clinical Translational Research. S.A.T. is supported by the Medical Scientist Training Program and a Rackham Pre-doctoral Award. This research was supported in part by National Institutes of Health Grant RO1 CA97063 (to A.M.C. and D.G.); U01 CA111275 (to A.M.C. and D.G.); P50 CA69568 (to A.M.C. and D.G.); and Department of Defense Grants PC040517 (to R.M.), PC051081 (to A.M.C. and S.V.), and PC060266 (to J.Y.). For V.E.M., this research was supported in part by the intramural research program of the NIH, Center for Cancer Research, NCI-Frederick. The Oncomine database was used initially in this manuscript. Oncomine is freely available to the academic community. Commercial rights to Oncomine have been licensed to Compendia Biosciences. A.M.C. is a cofounder of Compendia Biosciences and serves as head of the scientific advisory board. Funding Information: Prostate cancer tissues were collected from the Rapid Autopsy Program, which is part of the University of Michigan Prostate Cancer Specialized Program of Research Excellence (S.P.O.R.E.) Tissue Core. Tissue samples were collected with informed consent of the patients and prior Institutional Review Board approval. ",
year = "2007",
month = nov,
day = "13",
doi = "10.1016/j.ccr.2007.10.016",
language = "English (US)",
volume = "12",
pages = "419--431",
journal = "Cancer Cell",
issn = "1535-6108",
publisher = "Cell Press",
number = "5",
}