|
| Status |
Public on Dec 11, 2011 |
| Title |
Cooperation between Androgen Receptor and Polycomb in oncogenic transformation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
|
| Summary |
Androgen receptor (AR) is a hormone-activated transcription factor that plays important roles in prostate development, function, as well as malignant transformation. The downstream pathways of AR, however, are incompletely understood. AR has been primarily known as a transcriptional activator inducing prostate-specific gene expression. Through integrative analysis of genome-wide AR occupancy and androgen-regulated gene expression, here we report AR as a globally acting transcriptional repressor. This repression is mediated by androgen responsive elements (ARE) and dictated by Polycomb group protein EZH2 and repressive chromatin remodeling. In embryonic stem cells, AR-repressed genes are occupied by EZH2 and harbor bivalent H3K4me3 and H3K27me3 modifications that are characteristic of differentiation regulators, the silencing of which maintains the undifferentiated state. Concordantly, these genes are silenced in castration-resistant prostate cancer rendering a stem cell-like lack of differentiation and tumor progression. Collectively, our data reveal an unexpected role of AR as a transcriptional repressor inhibiting non-prostatic differentiation and, upon excessive signaling, resulting in cancerous de-differentiation. It provides an innovative mechanism for castration resistance and highlights novel therapeutic strategies to treat advanced prostate cancer.
Keywords: Genetic Modification
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| |
|
| Overall design |
compare gene expression in different cell lines with or without androgen treatment or EZH2 knockdown
|
| |
|
| Contributor(s) |
Yu J |
| Citation(s) |
22179855 |
| Submission date |
Sep 08, 2011 |
| Last update date |
Aug 13, 2018 |
| Contact name |
Jindan Yu |
| E-mail(s) |
jindan-yu@northwestern.edu
|
| Organization name |
Northwestern University
|
| Department |
Medicine - Hem/Onc
|
| Lab |
Yu
|
| Street address |
303 E. Superior St.
|
| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL10558 |
Illumina HumanHT-12 V4.0 expression beadchip |
|
| Samples (6)
|
| GSM791919 |
LNCaP_abl cells treated with ethanol for 48 hours |
| GSM791920 |
LNCaP_abl cells treated with R1881 for 48 hours |
| GSM791921 |
LNCaP cells hormone deprived and treated with ethanol for 48 hours |
| GSM791922 |
LNCaP cells hormone deprived and treated with R1881 for 48 hours |
| GSM791923 |
LnCaP cells treated with control non-targeting siRNA |
| GSM791924 |
LNCaP cells treated with siRNA targeting EZH2 |
|
| Relations |
| BioProject |
PRJNA144965 |
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