Journal
TRENDS IN ENDOCRINOLOGY AND METABOLISM
Volume 22, Issue 12, Pages 474-480Publisher
CELL PRESS
DOI: 10.1016/j.tem.2011.07.006
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Funding
- National Institute of Health [R00 CA126160, U54 CA113001]
- Ohio State University Comprehensive Cancer Center
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The androgen receptor (AR) is important for prostate cancer development and progression. Genome-wide mapping of AR binding sites in prostate cancer has found that the majority of AR binding sites are located within non-promoter regions. These distal AR binding regions regulate AR target genes (e.g. UBE2C) involved in prostate cancer growth through chromatin looping. In addition to long-distance gene regulation, looping has been shown to induce spatial proximity of two genes otherwise located far away along the genomic sequence and the formation of double-strand DNA breaks, resulting in aberrant gene fusions (e.g. TMPRSS2-ERG) that also contribute to prostate tumorigenesis. Elucidating the mechanisms of AR-driven chromatin looping will increase our understanding of prostate carcinogenesis and may lead to the identification of new therapeutic targets.
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