Abstract：
:Initially isolated as the dominant suppressor of the mutant epidermal growth factor receptor (ellipse), the Dachshund gene plays a key role in metazoan development regulating the Retinal Determination Gene Network. Herein, the DACH1 gene was expressed in normal prostate epithelial cells with reduced expression in human prostate cancer. DACH1 inhibited prostate cancer cellular DNA synthesis, growth in colony forming assays, and blocked contact-independent growth in soft agar assays. DACH1 inhibited androgen receptor (AR) activity, requiring a conserved DS Domain (Dachshund domain conserved with Ski/Sno) that bound NCoR/HDAC and was recruited to an androgen-responsive gene promoter. DACH1 inhibited ligand-dependent activity of AR mutations identified in patients with androgen-insensitive prostate cancer. The DS domain was sufficient for repression of the AR wild-type but failed to repress an AR acetylation site point mutant. These studies show a role for the Retinal Determination Gene Network in regulating cellular growth and signaling in prostate cancer.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Wu K,Katiyar S,Witkiewicz A,Li A,McCue P,Song LN,Tian L,Jin M,Pestell RGdoi
10.1158/0008-5472.CAN-08-3821subject
Has Abstractpub_date
2009-04-15 00:00:00pages
3347-55issue
8eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-08-3821journal_volume
69pub_type
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