Role of SRC-3delta4 in the Progression and Metastasis of Castration-Resistant Prostate Cancer
Abstract
SRC-3 delta 4, an N-terminus deletion isoform of steroid receptor coactivator (SRC-3), was shown to act as a signaling adaptor of EGF signaling in activating FAK. Its role in prostate cancer (PCa) progression is unclear. Interestingly, we found that SRC-3 delta 4 is upregulated in castration resistant PCa cells as compared to androgen-dependent PCa cells. As such, we determined whether SRC-3 delta 4 coactivates AR in an androgen-independent manner in response to EGF signaling. We have found that EGF stimulated the interaction of SRC-3 delta 4 with AR and SRC-3 4 nuclear localization in androgen-depleted culture conditions. In response to EGF stimulation, SRC-3 delta 4 was recruited to AR target genes promoters and regulated AR target genes transcription in an AR-dependent manner. Taken together, these results demonstrate that SRC-3 delta 4 acts as a coactivator of AR in the nucleus and regulates the transcription of AR target genes in response to EGF signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2012
- Accession Number
- ADA569694
Entities
People
- Weiwen Long
Organizations
- Baylor College of Medicine