Role of SRC-3delta4 in the Progression and Metastasis of Castration-Resistant Prostate Cancer
Abstract
SRC-3 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 4 is upregulated in castration resistant PCa cells as compared to androgen-dependent PCa cells. As such, we determined whether SRC-3 4 coactivates AR in an androgen-independent manner and promotes prostate cancer cell growth and invasiveness in response to EGF signaling. We have found that EGF stimulated the interaction of SRC-3 4 with AR, the recruitment of SRC-3 4 to the promoters of AR target genes, and AR target genes transcription in androgen-depleted culture conditions. In addition, SRC-3 4 promotes androgen-independent prostate cancer cell growth and invasion, during which EGF-induced phosphorylation of SRC-3 4 plays a critical role. Taken together, these results demonstrate that SRC-3 4 acts as a coactivator of AR and regulates the transcription of AR target genes and prostate cancer cell growth and invasion in response to EGF signaling.
Document Details
- Document Type
- Technical Report
- Publication Date
- Oct 01, 2013
- Accession Number
- ADA601314
Entities
People
- Weiwen Long
Organizations
- Baylor College of Medicine