A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth.
Journal: 2007/August - Molecular Cell
ISSN: 1097-2765
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 Oct1 that cooperate in mediating the androgen response. These collaborating factors, together with AR, form a regulatory hierarchy that governs androgen-dependent gene expression and prostate cancer growth and offer potential new opportunities for therapeutic intervention.
Relations:
Content
Citations
(274)
References
(40)
Diseases
(2)
Chemicals
(3)
Organisms
(1)
Processes
(5)
Anatomy
(1)
Affiliates
(2)
Similar articles
Articles by the same authors
Discussion board
Mol Cell 27(3): 380-392

A Hierarchical Network of Transcription Factors Governs Androgen Receptor-Dependent Prostate Cancer Growth

Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA 02115, USA
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, Boston, MA 02115, USA
Biomedicum Helsinki, Institute of Biomedicine (Physiology), University of Helsinki, FI-00014 Helsinki, Finland
Department of Pathology University of Michigan Medical School, Ann Arbor, MI 48109, USA
Department of Medicine University of Michigan Medical School, Ann Arbor, MI 48109, USA
Department of Urology University of Michigan Medical School, Ann Arbor, MI 48109, USA
Correspondence: ude.dravrah.icfd@nworb_selym

SUMMARY

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 Oct1 that cooperate in mediating the androgen response. These collaborating factors, together with AR, form a regulatory hierarchy that governs androgen-dependent gene expression and prostate cancer growth and offer potential new opportunities for therapeutic intervention.

SUMMARY

Footnotes

Supplemental Data

Supplemental Data include Supplemental Experimental Procedures, seven figures, and four tables and can be found with this article online at http://www.molecule.org/cgi/content/full/27/3/380/DC1/.

Accession Numbers

The microarray data in this study have been deposited in NCBI's Gene Expression Omnibus (GEO, http://www.ncbi.nlm.nih.gov/geo/) and are accessible under GEO Series accession number {"type":"entrez-geo","attrs":{"text":"GSE7868","term_id":"7868"}}GSE7868.

Footnotes

REFERENCES

REFERENCES
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.