Author/Authors :
Yu، نويسنده , , Jindan and Cao، نويسنده , , Qi and Mehra، نويسنده , , Rohit and Laxman، نويسنده , , Bharathi and Yu، نويسنده , , Jianjun and Tomlins، نويسنده , , Scott A. and Creighton، نويسنده , , Chad J. and Dhanasekaran، نويسنده , , Saravana M. and Shen، نويسنده , , Ronglai and Chen، نويسنده , , Guoan and Morris، نويسنده , , David S. and Marquez، نويسنده , , Victor E. and Shah، نويسنده , , Rajal B. and Ghosh، نويسنده , , Debashis and Varambally، نويسنده , , Sooryanarayana and Chinnaiyan، نويسنده , , Arul M. Chinnaiyan، نويسنده ,
Abstract :
Summary
lycomb 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.
