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| Status |
Public on May 05, 2007 |
| Title |
Suppression of androgen receptor mediated gene expression by a sequence-specific DNA binding polyamide |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by array
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| Summary |
Androgen Receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. We have designed a sequence-specific DNA binding polyamide (1) that targets the consensus androgen response element (ARE). This polyamide binds the PSA promoter ARE, inhibits androgen-induced expression of PSA and several other AR-regulated genes in cultured prostate cancer cells, and reduces AR occupancy at the PSA promoter and enhancer. Down-regulation of PSA by this polyamide was comparable to that produced by the synthetic anti-androgen bicalutamide (Casodex) at the same concentration. Genome-wide expression analysis reveals that a similar number of transcripts are affected by treatment with the polyamide and with bicalutamide. Direct inhibition of AR-DNA binding by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity. A polyamide (2) that targets a different DNA sequence is included as a control.
Keywords: Gene expression changes in cultured LNCaP cells after DHT-stimulation and various treatment conditions
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| Overall design |
DHT (dihydrotestosterone)-stimulated LNCaP cells that were treatment with polyamide 1, polyamide 2, bicalutamide were compared to control cells that were also DHT-stimulated. Cells not stimulated with DHT were also compared to the DHT-stimulated controls. Three biological replicates were included for each treatment/condition except the no-DHT induced controls, which were in biological duplicate.
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| Contributor(s) |
Dervan PB, Nickols NG |
| Citation(s) |
17566103 |
| Submission date |
May 04, 2007 |
| Last update date |
Mar 25, 2019 |
| Contact name |
Peter Dervan |
| Organization name |
California Institute of Technology
|
| Street address |
1200 East California Blvd
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| City |
Pasadena |
| State/province |
CA |
| ZIP/Postal code |
91125 |
| Country |
USA |
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| Platforms (1) |
| GPL570 |
[HG-U133_Plus_2] Affymetrix Human Genome U133 Plus 2.0 Array |
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| Samples (14)
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| Relations |
| BioProject |
PRJNA99843 |
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