Abstract B133: Regulation of the androgen receptor function by a metabolic kinase in prostate cancer.

In a recent genome-wide study to identify androgen receptor target genes we found that the AR promotes tumor growth by enhancing the expression and activity of enzymes required for metabolic biosynthesis. This raises the possibility for effective therapeutic approaches directed towards AR target genes. Kinases are well-established drug targets. In this study we identify androgen regulated kinome and show that an important androgen regulated metabolic kinase is a drug target in prostate cancer. Our proteome study shows that this kinase interacts with the androgen receptor and regulates AR stability. Inhibition of this kinase significantly reduces AR protein levels and suppresses prostate cancer growth in cell-lines and ex vivo cultures. In clinical prostate cancer this kinase is highly over-expressed in metastatic prostate cancers and inhibition represses metastatic potential of prostate cancer cells. Our study therefore establishes this kinase for the first time as an AR target gene that regualtes AR itself as part of feedback loop and makes a case for further investigation of its inhibitors as novel AR antagonists in both localised and advanced disease. Citation Information: Mol Cancer Ther 2013;12(11 Suppl):B133. Citation Format: Mohammad asim, Charlie Massie, Heather Zecchini, Ajoeb Baridi, Nelma Gomes, Hisham Mohammed, Vincent Zecchini, Basetti Madhu, Arham Qureshi, Roslin Russell, Wiebke Hessenkemper, Rouchelle Sriranjan, Carrie Yang, Andy Lynch, Elena Gregorengko, Rory Stark, Paul Rennie, John Griffiths, Aria Baniahmad, Jasol Carroll, Ian Mills, David Neal. Regulation of the androgen receptor function by a metabolic kinase in prostate cancer. [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference: Molecular Targets and Cancer Therapeutics; 2013 Oct 19-23; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2013;12(11 Suppl):Abstract nr B133.