Abstract 3309
Background
Prostate cancer is the second leading cause of cancer related deaths in men worldwide. Heat Shock Protein 90 (Hsp90) is expressed in tumour cells at high levels – 3-5% of total proteins – and regulates the function of oncogenes and other tumour related proteins. Protein kinase D3 (PKD3) has a proven role in the progression of androgen-independent prostate cancer. In the present study we set out to explore the impact of Hsp90 and PKD3, respectively, on prostate cancer growth and their potential interaction.
Methods
We employed the DU145 and PC3 well-characterized androgen-independent prostate cancer cell lines. Cell viability was determined by Trypan Blue exclusion cell counting. Apoptosis analysis was performed by flow cytometry after AnnexinV and propidium-iodide co-staining. Protein levels were detected by western blot and protein-protein interactions were investigated by co-immunoprecipitation.
Results
We found that the clinically used Hsp90 inhibitor ganetespib induced apoptosis and significantly reduced the viability of the androgen-independent DU145 and PC3 cell lines. The pan-PKD inhibitor CRT0066101 also decreased cell viability of the prostate cancer cells in a dose-dependent manner. Further, we demonstrated that ganetespib reduced PKD3 protein level in a concentration-dependent manner and induced its proteasomal degradation. Finally, a co-immunoprecipitation study revealed a physical connection between PKD3 and Hsp90.
Conclusions
We identified and confirmed an Hsp90-PKD3 chaperone client interaction, which may be important in prostate cancer cell survival. Further studies are under way to characterize the biological significance of our findings. Our results contribute to better understand the pathological signalling of androgen-independent prostate cancer cells and to find novel treatment strategies.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
MTA-SE Pathobiochemistry Research Group.
Funding
National Research, Development and Innovation Office - Hungary.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
5037 - CXCR4, CCR2 and CCR5 expression in subsets of tumor cells with stem and/or EMT features
Presenter: Olga Savelieva
Session: Poster Display session 1
Resources:
Abstract
5729 - Expression of mutant p53 affects cancer cell sensitivity to topotecan
Presenter: Rimma Mingaleeva
Session: Poster Display session 1
Resources:
Abstract
5725 - Breast cancer organoids a new tool for the prediction of drugs penetration and patient’outcome
Presenter: Giuseppina Roscigno
Session: Poster Display session 1
Resources:
Abstract
5680 - Aptamer-mediated exosomes detection for early breast cancer identification.
Presenter: Cristina Quintavalle
Session: Poster Display session 1
Resources:
Abstract
2460 - MicroRNA-181c promotes tamoxifen resistance in breast cancer cells via upregulation Akt/mTOR axis
Presenter: Alexander Scherbakov
Session: Poster Display session 1
Resources:
Abstract
3751 - Spatio-temporal separation of tumor infiltrating CD8+ T-cells and HER2/neu+ tumor cells in tumor-immune milieu of infiltrating ductal carcinoma of the breast
Presenter: Sandhya Sreedharan
Session: Poster Display session 1
Resources:
Abstract
4664 - Large genomic rearrangements in BRCA1 and BRCA2 genes in the Portuguese population.
Presenter: Joao Pinto
Session: Poster Display session 1
Resources:
Abstract
4611 - Non-BRCA1/2 hereditary breast and ovarian cancer: findings from a multidisciplinary program
Presenter: Ana Monteiro
Session: Poster Display session 1
Resources:
Abstract
5340 - Quantitative imaging and characterization of collagen patterns in high grade serous ovarian carcinoma (HGSOC)
Presenter: Ruby Huang
Session: Poster Display session 1
Resources:
Abstract
4209 - Semiquantitative assessment of vimentin expression in prostate cancer (PC)
Presenter: Marina Puchinskaya
Session: Poster Display session 1
Resources:
Abstract