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Title: Androgen Regulation of the TMPRSS2 Gene and the Effect of a SNP in an Androgen Response Element
Authors: Clinckemalie, Liesbeth
Spans, Lien
Dubois, Vanessa
Laurent, Michaƫl
Helsen, Christine
Joniau, Steven
Claessens, Frank # ×
Issue Date: Dec-2013
Publisher: Endocrine Society
Series Title: Molecular Endocrinology vol:27 issue:12 pages:2028-40
Article number: 10.1210/me.2013-1098
Abstract: More than 50% of prostate cancers have undergone a genomic reorganization that juxtaposes the androgen-regulated promoter of TMPRSS2 and the protein coding parts of several ETS oncogenes. These gene fusions lead to prostate-specific and androgen-induced ETS expression and are associated with aggressive lesions, poor prognosis, and early-onset prostate cancer. In this study, we showed that an enhancer at 13 kb upstream of the TMPRSS2 transcription start site is crucial for the androgen regulation of the TMPRSS2 gene when tested in bacterial artificial chromosomal vectors. Within this enhancer, we identified the exact androgen receptor binding sequence. This newly identified androgen response element is situated next to two binding sites for the pioneer factor GATA2, which were identified by DNase I footprinting. Both the androgen response element and the GATA-2 binding sites are involved in the enhancer activity. Importantly, a single nucleotide polymorphism (rs8134378) within this androgen response element reduces binding and transactivation by the androgen receptor. The presence of this SNP might have implications on the expression and/or formation levels of TMPRSS2 fusions, because both have been shown to be influenced by androgens.
URI: 
ISSN: 0888-8809
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Gerontology and Geriatrics
Laboratory of Molecular Endocrinology
× corresponding author
# (joint) last author

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