A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth
- PMID: 17679089
- PMCID: PMC3947890
- DOI: 10.1016/j.molcel.2007.05.041
A hierarchical network of transcription factors governs androgen receptor-dependent prostate cancer growth
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.
Figures
![Figure 1](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0001.gif)
![Figure 2](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0002.gif)
![Figure 3](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0003.gif)
![Figure 4](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0004.gif)
![Figure 5](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0005.gif)
![Figure 6](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0006.gif)
![Figure 7](https://cdn.statically.io/img/www.ncbi.nlm.nih.gov/pmc/articles/instance/3947890/bin/nihms-126328-f0007.gif)
Similar articles
-
Androgen receptor enhancer usage and the chromatin regulatory landscape in human prostate cancers.Endocr Relat Cancer. 2019 May;26(5):R267-R285. doi: 10.1530/ERC-19-0032. Endocr Relat Cancer. 2019. PMID: 30865928 Review.
-
Integration of cap analysis of gene expression and chromatin immunoprecipitation analysis on array reveals genome-wide androgen receptor signaling in prostate cancer cells.Oncogene. 2011 Feb 3;30(5):619-30. doi: 10.1038/onc.2010.436. Epub 2010 Oct 4. Oncogene. 2011. PMID: 20890304
-
Amyloid precursor protein is a primary androgen target gene that promotes prostate cancer growth.Cancer Res. 2009 Jan 1;69(1):137-42. doi: 10.1158/0008-5472.CAN-08-3633. Cancer Res. 2009. PMID: 19117996
-
Identification of novel androgen response genes in prostate cancer cells by coupling chromatin immunoprecipitation and genomic microarray analysis.Oncogene. 2007 Jun 28;26(30):4453-63. doi: 10.1038/sj.onc.1210229. Epub 2007 Feb 5. Oncogene. 2007. PMID: 17297473
-
Androgen receptor action in hormone-dependent and recurrent prostate cancer.J Cell Biochem. 2006 Oct 1;99(2):362-72. doi: 10.1002/jcb.20811. J Cell Biochem. 2006. PMID: 16619264 Review.
Cited by
-
Patient-derived castration-resistant prostate cancer model revealed CTBP2 upregulation mediated by OCT1 and androgen receptor.BMC Cancer. 2024 May 2;24(1):554. doi: 10.1186/s12885-024-12298-3. BMC Cancer. 2024. PMID: 38698344 Free PMC article.
-
ERG activates a stem-like proliferation-differentiation program in prostate epithelial cells with mixed basal-luminal identity.bioRxiv [Preprint]. 2024 Apr 6:2023.05.15.540839. doi: 10.1101/2023.05.15.540839. bioRxiv. 2024. PMID: 38585869 Free PMC article. Preprint.
-
Genome-wide analysis of plant specific YABBY transcription factor gene family in carrot (Dacus carota) and its comparison with Arabidopsis.BMC Genom Data. 2024 Mar 5;25(1):26. doi: 10.1186/s12863-024-01210-4. BMC Genom Data. 2024. PMID: 38443818 Free PMC article.
-
The androgen receptor interacts with GATA3 to transcriptionally regulate a luminal epithelial cell phenotype in breast cancer.Genome Biol. 2024 Feb 5;25(1):44. doi: 10.1186/s13059-023-03161-y. Genome Biol. 2024. PMID: 38317241 Free PMC article.
-
Validating a re-implementation of an algorithm to integrate transcriptome and ChIP-seq data.PeerJ. 2023 Oct 20;11:e16318. doi: 10.7717/peerj.16318. eCollection 2023. PeerJ. 2023. PMID: 37876906 Free PMC article.
References
-
- Balk SP, Ko YJ, Bubley GJ. Biology of prostate-specific antigen. J. Clin. Oncol. 2003;21:383–391. - PubMed
-
- Boyes J, Byfield P, Nakatani Y, Ogryzko V. Regulation of activity of the transcription factor GATA-1 by acetylation. Nature. 1998;396:594–598. - PubMed
-
- Carroll JS, Liu XS, Brodsky AS, Li W, Meyer CA, Szary AJ, Eeckhoute J, Shao W, Hestermann EV, Geistlinger TR, et al. Chromosome-wide mapping of estrogen receptor binding reveals long-range regulation requiring the forkhead protein FoxA1. Cell. 2005;122:33–43. - PubMed
-
- Carroll JS, Meyer CA, Song J, Li W, Geistlinger TR, Eeckhoute J, Brodsky AS, Keeton EK, Fertuck KC, Hall GF, et al. Genome-wide analysis of estrogen receptor binding sites. Nat. Genet. 2006;38:1289–1297. - PubMed
-
- Cirillo LA, Lin FR, Cuesta I, Friedman D, Jarnik M, Zaret KS. Opening of compacted chromatin by early developmental transcription factors HNF3 (FoxA) and GATA-4. Mol. Cell. 2002;9:279–289. - PubMed
Publication types
MeSH terms
Substances
Associated data
- Actions
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases
Research Materials