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| Status |
Public on May 18, 2010 |
| Title |
An Integrated Network of Androgen Receptor and TMPRSS2-ERG Gene Fusion in Prostate Cancer Progression (I) |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Androgen receptor (AR) is a transcription factor that plays a central role in the growth and development of the normal prostate and its malignant transformation. More recently, a majority of prostate cancers have been shown to harbor recurrent gene fusions of the androgen-regulated gene, TMPRSS2, to the oncogenic ETS transcription factor ERG. Here we employed chromatin immunoprecipitation coupled to massively parallel sequencing (ChIP-Seq) to explore the genome-wide localization of these transcription factors in human prostate cancer cell lines as well as tissues. Unexpectedly, transcriptional networks emanating from AR and ERG were found to be highly overlapping. Furthermore, AR was found to regulate known 5’ fusion partners in prostate cancer including TMPRSS2, as well as negatively regulating its own expression. While induced by androgen through fusion to TMPRSS2, ERG itself was shown to inhibit AR expression and positively regulate the genomic locus of wild-type ERG, thus revealing multiple levels of molecular cross-talk between AR and ERG. Importantly, androgen-sensitive prostate cancer cells in which ERG is overexpressed are able to proliferate and invade in the absence of androgen. Thus, we dissected the intertwined genomic landscape of two master transcriptional regulators of prostate cancer and suggest a role for ERG in maintaining transcriptional networks necessary for androgen-independent prostate cancer growth. These studies may suggest that future therapies against prostate cancer should target both AR and ERG, rather than AR alone, in order to achieve maximum effectiveness.
Keywords: Genetic modification
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| Overall design |
time-course analysis of androgen treatment in LNCaP cells, and analysis of ERG overexpression and androgen effect in VCaP cells
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| Contributor(s) |
Yu J, Chinnaiyan AM |
| Citation(s) |
20478527 |
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| Submission date |
Dec 17, 2008 |
| Last update date |
Feb 22, 2018 |
| Contact name |
Jindan Yu |
| E-mail(s) |
jindan-yu@northwestern.edu
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| Organization name |
Northwestern University
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| Department |
Medicine - Hem/Onc
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| Lab |
Yu
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| Street address |
303 E. Superior St.
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| City |
Chicago |
| State/province |
IL |
| ZIP/Postal code |
60611 |
| Country |
USA |
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| Platforms (1) |
| GPL4133 |
Agilent-014850 Whole Human Genome Microarray 4x44K G4112F (Feature Number version) |
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| Samples (15)
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| GSM352226 |
LnCaP cells treated with R1881 for 3 hours |
| GSM352227 |
LnCaP cells treated with R1881 for 6 hours |
| GSM352228 |
LnCaP cells treated with R1881 for 12 hours |
| GSM352229 |
LnCaP cells treated with R1881 for 24 hours |
| GSM352230 |
LnCaP cells treated with R1881 for 48 hours |
| GSM352231 |
VCaP cells treated with ethanol and infected with LacZ |
| GSM352232 |
VCaP cells treated with ethanol and infected with ERG |
| GSM352233 |
VCaP cells treated with R1881 |
| GSM352234 |
VCaP cells treated with R1881 and infected with LacZ |
| GSM352235 |
VCaP cells treated with R1881 and infected with ERG |
| GSM352236 |
VCaP cells treated with ethanol and infected with LacZ, dye swap |
| GSM352237 |
VCaP cells treated with ethanol and infected with ERG, dye swap |
| GSM352238 |
VCaP cells treated with R1881, dye swap |
| GSM352239 |
VCaP cells treated with R1881 and infected with LacZ, dye swap |
| GSM352240 |
VCaP cells treated with R1881 and infected with ERG, dye swap |
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| This SubSeries is part of SuperSeries: |
| GSE14097 |
An Integrated Network of Androgen Receptor and TMPRSS2-ERG Gene Fusion in Prostate Cancer Progression |
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| Relations |
| BioProject |
PRJNA114539 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE14028_RAW.tar |
220.0 Mb |
(http)(custom) |
TAR (of TXT) |
| Processed data included within Sample table |
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