Dinuka DeSilva
Preceptors: Young Whang, MD, PhD, Shelton Earp, MD
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Reactivation of androgen receptor (AR) is critical to castration resistant progression of prostate cancer. Intracellular tyrosine kinase Ack1 (cdc42 associated tyrosine kinase) activation is associated with the conversion of poorly tumorigenic prostate cancer cells, LNCaP, into aggressive, invasive, androgen independent tumors in nude mice. Our lab has shown that Ack1 phosphorylates AR that results in androgen independent activation and downstream enhancement of AR-dependent gene expression. Furthermore, our lab identified SLIRP (SRA stem-loop interacting RNA binding protein) as an AR binding protein that is regulated by Ack1. The data from our studies suggest that SLIRP acts as a transcriptional repressor of AR induced gene expression. Additionally, Ack1 induces dissociation of SLIRP from AR and this may facilitate AR-dependent transcription. Hence, SLIRP dissociation by Ack1 signaling may be a mechanism by which AR is reactivated in hormone refractory prostate cancer. My project focuses on characterizing the role of SLIRP in prostate cancer cell growth and AR transcription and elucidating the mechanism of Ack1 disruption of the AR-SLIRP complex by identifying binding partners of the SLIRP co-repressor complex.
