Poster Presentation 29th Lorne Cancer Conference 2017

Characterisation of copper homeostasis proteins in normal and cancerous prostate (#143)

Sharnel AS Clatworthy 1 , Delphine Denoyer 1 , Michael A Cater 1 2
  1. Centre for Cellular and Molecular Biology, School of Life and Environmental Sciences, Deakin University, Burwood, VIC, Australia
  2. Department of Pathology, University of Melbourne, Parkville, VIC, Australia

We previously demonstrated that prostate adenocarcinoma development in TRAMP (Transgenic Adenocarcinoma of Mouse Prostate) mice requires a functional supply of serum copper, and is significantly impeded by altered systemic copper distribution1. However, the copper biology of the prostate gland is relatively unknown. Therefore, we identified copper-transporters that are expressed in human and mouse prostates. The primary mammalian copper-transporters include the influx transporters, CTR1 and CTR2, and the efflux transporters, ATP7A and ATP7B. Previous studies have confirmed the presence of both CTR1 and ATP7A in normal human prostatic tissues2,3. We characterized the copper-transporters in human and mouse prostate using quantitative polymerase chain reaction (qPCR) and western blot analysis. The mRNA and protein expression of CTR1, CTR2 and ATP7A were confirmed and compared with their expression in other well-characterized tissues (e.g. liver and kidney). Notably, we did not detect expression of ATP7B in the prostate. Additionally, we found markedly higher levels of CTR2 expression (both transcript and protein) in the prostate when compared to other tissues. CTR2 forms a transmembrane homotrimeric structure and can modulate intracellular copper levels in part by regulating CTR1. The prostate has comparatively little intracellular copper and we propose that high levels of CTR2 are required to moderate copper influx by CTR1. We are further characterizing the expression of copper-transporters throughout prostate cancer progression.

  1. Denoyer, D. et al. Copper as a target for prostate cancer therapeutics: copper-ionophore pharmacology and altering systemic copper distribution. Oncotarget, doi:10.18632/oncotarget.9245 (2016).
  2. Samimi, G. et al. Increase in Expression of the Copper Transporter ATP7A during Platinum Drug-Based Treatment Is Associated with Poor Survival in Ovarian Cancer Patients. Clinical Cancer Research 9, 5853-5859 (2003).
  3. Holzer, A. K. et al. Expression of the human copper influx transporter 1 in normal and malignant human tissues. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 54, 1041-1049, doi:10.1369/jhc.6A6970.2006 (2006).