Abstract A29: Heterogeneity of androgen receptor dynamics and drug response in prostate cancer cells

Abstract

Abstract Background: Recent studies suggest that the spatio-temporal dynamics of critical signaling molecules can mediate heterogeneous response to therapeutic intervention. Here, we set out to apply live cell imaging of single cells in high throughput to correlate the dynamics of androgen receptor (AR) with response to taxane chemotherapy in heterogeneous prostate cancer (PCa) cell populations. Methods: We previously developed a 3-step high throughput imaging and data analysis workflow to improve measurements of the dynamic phenotype in heterogeneous populations. We treated PCa cells stably expressing GFP-AR with AR ligand and quantified nuclear/cytoplasmic GFP intensity to measure nuclear translocation of AR over a 30 min time course. Then we treated cells with paclitaxel and tracked cells' response for 24h. Results: Applied to PCa cell lines stably expressing GFP-AR, we measured considerable heterogeneity of AR translocation in response to ligand stimulation. We quantified populations of non-responders and classified responding cells based on the dynamics of AR. Evaluation of cell morphology revealed a fraction of relatively large cells to be exclusively slow responders to AR ligand. We measured heterogeneous response to treatment with paclitaxel that correlated with cell phenotype. Conclusion: We conclude that cell morphology features in heterogeneous PCa cell populations correlate with AR translocation dynamics and drug response. Future experiments will include expression of the constitutively active AR variant AR-v7 to analyze its effect on the dynamics of wild-type AR and on single cell response to paclitaxel chemotherapy. Note: This abstract was not presented at the conference. Citation Format: Katherin Patsch, Anjana Soundararajan, Mark Engeln, Mitchell E. Gross, Shannon M. Mumenthaler, Daniel Ruderman. Heterogeneity of androgen receptor dynamics and drug response in prostate cancer cells. [abstract]. In: Proceedings of the AACR Special Conference on Engineering and Physical Sciences in Oncology; 2016 Jun 25-28; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2017;77(2 Suppl):Abstract nr A29.