A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth

Qianben Wang, Wei Li, X. Shirley Liu, Jason Carroll, Olli Jänne, Erika Keeton, Arul Chinnalyan, Kenneth Pienta, Myles Brown

Research output: Contribution to journalArticleScientificpeer-review

Abstract

Androgen receptor (AR) is a ligand -dependent transcription factor that plays a key role in prostate cancer. Little is known about the nature of AR cis-regulatory sites in the human genome. We have mapped the AR binding regions on two chromosomes in human prostate cancer cells by combining chromatin immunoprecipitation (ChIP) with tiled oligonucleotide microarrays. We find that the majority of AR binding regions contain noncanonical AR-responsive elements (AREs). Importantly, we identify a noncanonical ARE as a cis-regulatory target of AR action in TMPRSS2, a gene fused to ETS transcription factors in the majority of prostate cancers. In addition, through the presence of enriched DNA-binding motifs, we find other transcription factors including GATA2 and Octl that cooperate in mediating the androgen response. These collaborating factors, together with AR, form a regulatory hierarchy that governs androgendependent gene expression and prostate cancer growth and offer potential new opportunities for therapeutic intervention.
Original languageEnglish
JournalMolecular Cell
Volume27
Pages (from-to)380-392
Number of pages13
ISSN1097-2765
DOIs
Publication statusPublished - 2007
MoE publication typeA1 Journal article-refereed

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