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Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10418-23. Epub 2007 Jun 12.

Suppression of androgen receptor-mediated gene expression by a sequence-specific DNA-binding polyamide.

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1
Division of Chemistry and Chemical Engineering, California Institute of Technology, Pasadena, CA 91125, USA.

Abstract

Androgen receptor (AR) is essential for the growth and progression of prostate cancer in both hormone-sensitive and hormone-refractory disease. A DNA-binding polyamide that targets the consensus androgen response element binds the prostate-specific antigen (PSA) promoter androgen response element, 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 antiandrogen 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 the AR-DNA interface by sequence-specific DNA binding small molecules could offer an alternative approach to antagonizing AR activity.

PMID:
17566103
PMCID:
PMC1965528
DOI:
10.1073/pnas.0704217104
[Indexed for MEDLINE]
Free PMC Article
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