Small Molecule Inhibitors of ERG and ETV1 in Prostate Cancer
Abstract
A group of chromosomal translocations were recently discovered in prostate cancer that fuses the 5` region of TMPRSS2 (a serine protease) gene to the 3` region of ETS transcription factor genes (1). TMPRSS2 is an androgen responsive gene and contributes only its promoter region and usually a very short exon-1 (2, 3). This causes aberrant expression of an ETS transcription factor in response to androgen. The most common ETS member involved in prostate cancer chromosomal translocations is ERG but other members such as ETV1, ETV4 and ETV5 have been also observed (4, 5). The more aggressive prostate cancers often contain these translocations, thus potentially increasing their utility as both diagnostic and prognostic marker (6-8). Cell culture and transgenic animal models suggest that increased expression of ETS members, as a result of the chromosomal translocations, increase cell invasion without affecting the proliferative potential (9-11). However, in some xenograft models reducing expression of TMPRSS2-ERG protein slows down prostate cancer growth (12, 13). Therefore, ETS proteins emerge as potential novel targets for treatment of primary and/or metastatic disease in prostate cancer.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2014
- Accession Number
- ADA613409
Entities
People
- Colm Morrissey
Organizations
- University of Washington