Prostate Cancer Therapeutics Group - Adelaide Prostate Cancer Research Centre-Discipline of Medicine6

Lead Researchers:
Dr Lisa Butler
Dr Margaret Centenera
Professor Wayne Tilley

Contact person :

Dr Lisa Butler
Telephone: 82223225
Email

Prostate Cancer Therapeutics Group - Adelaide Prostate Cancer Research Centre

Dr Lisa Butler and Dr Margaret Centenera

Our research is a fusion of cancer biology and endocrinology, focusing on new therapies for prostate cancer. At the cellular level we investigate how hormones and potential new therapeutics influence cancer cell growth and apoptosis. We have unique models of cancer, including cancer tissue from patients that is cultured ex vivo, to further investigate hormone signalling, molecular mechanisms and potential new treatments in cancer. We also use a broad range of molecular and cellular techniques and the latest technologies to investigate how genes, proteins and epigenetic modifications influence cellular function. These techniques include real time PCR, western blotting, chromatin immunoprecipitation, whole genome expression analysis, immunohistochemistry, confocal microscopy, cloning, transfection and siRNA gene knockdown.

Model of prostate cancer used to investigate novel agents

Research Projects

Developing New Therapeutic Approaches for Prostate Cancer

Androgen signalling is essential for the development and maintenance of the prostate gland, and has been linked to all stages of prostate cancer (PCa). When mediated by the androgen receptor (AR), androgen signaling remains the major determinant of PCa progression, making the AR a viable therapeutic target. In this project, the anti-tumour activity and toxicity of novel AR-targeted agents alone or in combination with current PCa agents will be compared to current agents alone. Initially, growth and proliferation of PCa cells in culture will be compared. The agents will be further investigated in vivo for their ability to prevent or delay tumour growth using a mouse model of PCa. In addition, we will investigate the mechanisms of action of these AR-targeted agents, using cell-death and cell cycle studies, and Affymetrix microarray to identify genes that are modulated by the treatment. These studies will provide proof of concept for future clinical trials of AR-targeted therapies in PCa.

Key References

Centenera MM, Harris JM, Tilley WD, Butler LM. The contribution of different androgen receptor domains to receptor dimerization and signaling. Mol Endocrinol 22: 2373-2382, 2008.
Marrocco DL, Tilley WD, Bianco-Miotto T, Evdokiou A, Scher HI, Rifkind RA, Marks PA, Richon VM and Butler LM. Suberoylanilide hydroxamic acid (SAHA; vorinostat) represses androgen receptor expression and acts synergistically with an androgen receptor antagonist to inhibit prostate cancer cell proliferation. Mol Cancer Ther 6: 51-60, 2007.
Butler LM, Centenera MM, Neufing PJ, Buchanan G, Choong CSY, Ricciardelli C, Saint K, Lee M, Ochnik A, Yang M, Brown MP and Tilley WD. Inhibitory receptor variants suppress androgen receptor signaling in prostate cancer cells. Mol Endocrinol 20: 1009-1024, 2006.
Buchanan G, Ricciardelli C, Harris JM, Prescott J, Yu Z C-L, Jia L, Butler LM, Marshall VR, Scher HI, Gerald WL, Coetzee GA, Tilley WD. Control of androgen receptor signaling in prostate cancer by the co-chaperone small glutamine-rich tetratricopeptide repeat containing protein alpha. Cancer Res 67: 10087-96, 2007.
Scher HI, Buchanan G, Gerald W, Butler LM, Tilley WD. Targeting the androgen receptor: improving outcomes for castration resistant prostate cancer. Endocr Relat Cancer 11: 459-476, 2004.

Prostate Cancer Therapeutics Group - Adelaide Prostate Cancer Research Centre

Postgraduate Research 2012

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