Adelaide Prostate Cancer BioResource Consortium

Chief Investigators

Professor Wayne Tilley, Head, Dame Roma Mitchell Cancer Research Laboratories¹.
Professor Villis Marshall, Director, Surgical Specialties Service^1,2.
Professor Howard Morris, Director, Hanson Institute³.
Professor Tom Dodd, Head, Tissue Pathology⁴.
Associate Professor David Horsfall, Project Manager, APCC BioResource¹.
Dr Lisa Butler, RAH/IMVS Florey Fellow¹.
Dr Grant Buchanan, NHMRC CJ Martin Fellow¹.
Dr Tina Bianco-Miotto, NHMRC Peter Doherty Fellow¹.
Dr Michael Brown, Head, Medical Oncology⁵.
Dr Penny Cohen, Pathologist⁴.
Dr Carmela Ricciardelli, The Cancer Council SA Senior Research Fellow⁶.
Dr Andrew Sakko, The Cancer Council SA W Bruce Hall Cancer Research Fellow¹.
Dr Jeffrey Barrett, Post-Doctoral Fellow¹.
Dr Jurgen Stahl, Pathologist⁷.
Dr Alan Stapleton, Urologist ^2,8.
Dr Peter Sutherland, Urologist².
Stephen Nygaard, Scientist⁴.
Helen Hughes, Research Nurse¹, APCC BioResource Node Coordinator

Affiliations

1. Dame Roma Mitchell Cancer Research Laboratory, Adelaide University/Hanson Institute

2. Surgery, Royal Adelaide Hospital

3. Endocrine Bone Laboratory, Hanson Institute

4. Tissue Pathology, Institute of Medical and Veterinary Sciences

5. Medical Oncology, Royal Adelaide Hospital

6. Obstetrics and Gynaecology, Adelaide University

7. Adelaide Pathology Partners

8. Surgery, Repatriation General Hospital, Daw Park

Research Activity

The Adelaide prostate cancer research group is involved in studying many aspects of prostate cancer, including disease susceptibility, progression and new therapeutic strategies. A particular focus is the mechanism(s) of disease progression in patients treated by surgery for clinically localised disease, and in patients treated with androgen ablation therapy (castration or drug-induced) for advanced disease where the cancer has spread to the bones. During the course of androgen ablation therapy, most tumours become resistant to treatment. Although this involves diverse cellular pathways, many of these pathways interact with the androgen receptor, a key cellular mediator of the effects of testicular androgens in prostate cancer cells. Studies of the androgen receptor pathway, and other pathways involved in regulating cancer cell motility and tissue invasion, have identified new targets to ablate androgen control of cancer growth as well as new treatment strategies that are currently being investigated in clinical trials. 

There is considerable epidemiological evidence that men with a low vitamin D status have an increased risk for developing prostate cancers. The Adelaide group are studying the transcriptional control of vitamin D metabolism, and the effect of vitamin D status on the development of the prostate gland using rodent models.

Major Prostate Cancer Grants (last 5 years)

• Characterisation of alterations in the androgen signalling axis that contribute to treatment failure in prostate cancer. 2000-2002, $380,000, NHMRC; Tilley WD and Marshall. VR

• Androgen-regulated proteins: predictors of prostate cancer development and progression. 2001-2003, $245,000, NHMRC; Choong CS, Horsfall DJ, Tilley WD and Marshall VR.

• Geldanamycin derivatives: novel inhibitors of androgen signalling for the treatment of metastatic prostate cancer. 2002-2004, $315,000, NHMRC; Tilley WD and Marshall. VR

• Dominant negative androgen receptors: a novel approach to the treatment of metastatic prostate cancer. 2002-2003, $126,416. The Cancer Council of South Australia, Tilley WD, Neufing P, Butler LM, Yang M.

• Geldanamycin analogs: effects on wild-type and mutant androgen receptor function. 2003, $200,000. CaPCURE, Rosen N, Scher H, Tilley WD.

• Modulation of prostate cancer cell attachment to stromal matrix by versican. 2003, $69,658. Cancer Council South Australia, Horsfall DJ.

• A cohort study of health and aging in North West Adelaide men. 2004-2006, $450,000. University of Adelaide, Florey Foundation, Wittert G, Marshall VR, Hiller J, Warin M, Taylor A, O’Loughlin P, Tilley WD, Choong CS, Wallace J.

• Androgen receptor signalling and progression of prostate cancer. 2004–2006, $455,250. NHMRC, Tilley WD, Butler LM and Marshall VR.

• Versican: a cell motility-promoting proteoglycan pivotal for prostate cancer metastasis. 2004-2005, $148,034. Cancer Council South Australia, Horsfall DJ, Tilley WD.

• Australian Prostate Cancer Collaboration (APCC) BioResource. 2004-2009, $2.1million. NHMRC Enabling Grant, Clements J, Sutherland R, Risbridger G and Tilley WD

• Prostate cancer cell synthesis of 1,25 dihydroxyvitamin D and cell growth. 2005-2006, $168,000. Cancer Council of South Australia, Morris HA, May BK, Tilley WD.

• Prognostic importance of androgen receptors in epithelium and  stroma in early stage prostate cancer. 2005-2007, $343,000. NHMRC, Horsfall DJ, Marshall VR, Ricciardelli C, Tilley WD.

• Androgen receptor signalling in development and progression of prostate cancer. 2007–2009, $723,750. NHMRC, Tilley WD, Butler LM and Marshall VR.

Selected Prostate Cancer Related Publications (last 5 years)

               Book Chapters:

• Tilley WD, Buchanan G and Coetzee GA. Hormones and Cancer. Androgen receptor signaling in prostate cancer. In: Hormones and Cancer. (Eds. Henderson, Ponder and Ross). Oxford University Press pp 288-315, 2003.

• Beekman KW, Buchanan G, Tilley WD, Scher HI. Beyond first line hormones: options for castration-resistant disease. In: Comprehensive Textbook of Genitourinary Oncology. (Eds. Vogelzang NJ, Scardina PT, Shipley WU, Coffey D). Wiley and Williams, Lippincott, Philadelphia  pp 330-340, 2005.

• Beekman KW, Buchanan G, Tilley WD, Scher HI. Anti-Androgen Withdrawal Syndromes: Pathophysiology and Clinical Implications. In: Prostate Cancer: Principles and Practice. (Ed. Partin AW). Lippincott, Philadelphia (in press).

         Journal articles:

• Buchanan G, Irvine RA, Coetzee GA, Tilley WD. Contribution of the androgen receptor to prostate cancer predisposition and progression. Cancer Metastasis Rev. 20: 207-223, 2002.

• Jackson MW, Roberts JS, Heckford SE, Ricciardelli C, Stahl J, Choong, C, Horsfall DH and Tilley WD. A potential autocrine role for vascular endothelial growth factor in prostate cancer. Cancer Res. 62: 854-859, 2002.

• Alaina J, James IUA, Harris JM, Buchanan G, Tilley WD, Marcelli M, Lamb DJ and Weigel NL.  A novel androgen receptor mutant, A748T, exhibits hormone concentration-dependent defects in nuclear accumulation and activity despite normal hormone-binding affinity.  Mol. Endocrinol. 16: 2692-2705, 2002.

• Jia L, Kim J, Shen H, Clark PE, Tilley WD and Coetzee GA. Androgen receptor activity at the prostate specific antigen locus: steroidal and non-steroidal mechanisms. Mol Cancer Res. 5: 385-392, 2003.

• Kim J, Jia L, Tilley WD and Coetzee GA. Dynamic methylation of histone H3 at lysine 4 in transcriptional regulation by the androgen receptor. Nucl Acids Res 31: 6741-6747, 2003

• Severi G, Giles GG, Southey MC, Tesoriero A, Tilley WD, Neufing P, Morris H, English DR, McCredie MRE, Boyle P and Hopper JL. ELAC2/HPC2 polymorphisms are not associated with prostate cancer or serum prostate-specific antigen level. J. Natl. Cancer Inst. 95: 818-824, 2003.

• Sakko AJ, Ricciardelli C, Mayne K, Suwiwat S, LeBaron RG, Marshall VR, Tilley WD and Horsfall DJ. Modulation of prostate cancer cell attachment to matrix by versican. Cancer Res. 63: 4786-4791, 2003.

• Zhang L, Brereton HM, Hahn M, Froscio M, Tilley WD, Brown MP and Barritt GJ.  Expression of the Drosophila transient receptor potential-like (TRPL) Ca²⁺ channel protein in a prostate cancer cell line decreases cell survival. Cancer Gene Ther. 10: 611-625, 2003.

• Hall RE, Horsfall DJ, Stahl J, Vivekanandan S, Ricciardelli C, Stapleton AMF, Scardino PT, Neufing P, and Tilley WD. Apolipoprotein-D: a novel cellular marker for HGPIN and prostate cancer. Prostate 58: 103-8, 2004.

• Buchanan G, Craft PS, Yang M, Cheong A, Prescott J, Jia L, Coetzee GA and Tilley WD. PC-3 cells with enhanced androgen receptor signalling: a model for clonal selection in prostate cancer. Prostate 60: 352-366, 2004.

• Buchanan G, Yang M, Cheong A, Harris J, Irvine R, Lambert P, Moore N, Raynor M, Neufing P, Coetzee G and Tilley WD. Structural and functional consequences of glutamine tract variation in the androgen receptor. Hum Mol Genet 13: 1677-1692, 2004.

• Jia L, Choong C, Ricciardelli C, Tilley WD and Coetzee GA. Androgen receptor signalling: mechanism of IL-6 inhibition. Cancer Res 64:2619-2626, 2004.

• Scher H, Buchanan G, Gerald W, Butler LM, and Tilley WD. Targeting the androgen receptor: improving outcomes for castration resistant prostate cancer. Endocr Relat  Cancer 11: 459-476, 2004.

• Shen HC, Buchanan G, Butler LM, Prescott J, Henderson M, Tilley WD, Coetzee GA. GRIP1 mediates the interaction between amino- and carboxyl-termini of the androgen receptor. Biol Chem. 386: 69-74, 2005.

• Han G, Buchanan G, Harris JM, Ittmann M, Yu X, DeMayo FJ, Tilley WD, Greenberg NM. Mutation of the androgen receptor causes oncogenic transformation of the prostate. Proc Natl Acad Sci USA. 102:1151-1156, 2005.

• Ricciardelli C, Choong CS, Buchanan G, Vivekanandan S, Neufing P, Stahl J, Marshall VR, Horsfall DJ, Tilley WD. Androgen receptor levels in prostate cancer epithelial and peritumoral stromal cells identify non-organ confined disease. Prostate. 63:19-28, 2005.

• Makridakis NM, Buchanan G, Tilley WD, Reichardt JK. Androgen metabolic genes in prostate cancer predisposition and progression. Frontiers in Bioscience. 10:2892-2903, 2005.

• Severi G, Hayes VM, Neufing P, Padilla EJ, Tilley WD, Eggleton SA, Morris HA, English DR, Southey MC, Hopper JL, Sutherland RL, Boyle P, Giles GG. Variants in the prostate-specific antigen (PSA) gene and prostate cancer risk, survival, and circulating PSA. Cancer Epidemiol Biomarkers Prev. 15:1142-1147, 2006.

• Severi G, Morris HA, MacInnis RJ, English DR, Tilley WD, Hopper JL, Boyle P, Giles GG. Circulating insulin-like growth factor-I and binding protein-3 and risk of prostate cancer. Cancer Epidemiol Biomarkers Prev. 15:1137-1141, 2006.

• Butler LM, Centenera MM, Neufing PJ, Buchanan G, Choong CS, Ricciardelli C, Saint K, Lee M, Ochnik A, Yang M, Brown MP, Tilley WD. Suppression of androgen receptor signaling in prostate cancer cells by an inhibitory receptor variant. Mol Endocrinol. 20:1009-1024, 2006.

         International Patents

• 5,804,386 USA, 1998. Tilley WD. Prostate cancer screening method which utilizes measurement of apolipoprotein-D levels in body fluids.

• WO03/070 Multiple Countries, 2003. Butler LM, Richon VM, Rifkind RA, Marks PA. Method of treating TRX mediated diseases.

• US2003235588 USA, 2003. Butler LM, Richon VM, Rifkind RA, Marks PA. Method of treating TRX mediated diseases.