Role of SRC-3delta4 in the Progression and Metastasis of Castration-Resistant Prostate Cancer
Final rept. 30 Sep 2011-29 Sep 2014
BAYLOR COLL OF MEDICINE HOUSTON TX
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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 and promotes prostate cancer cell growth and invasiveness in response to EGF signaling. We have found that EGF stimulated the interaction of SRC-3 delta 4 with AR, the recruitment of SRC-3 delta 4 to the promoters of AR target genes, and AR target genes transcription in androgen-depleted culture conditions. In addition, SRC-3 delta promotes androgen-independent prostate cancer cell growth and invasion, during which EGF-induced phosphorylation of SRC-3 delta plays a critical role. Taken together, these results demonstrate that SRC-3 delta 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.
- Medicine and Medical Research