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
4526 - Long-term outcome of neoadjuvant tyrosine kinase inhibitors (TKI) in locally advanced dermatofibrosarcoma protuberans (DFSP)
Presenter: Jessica Beaziz
Session: Poster Display session 1
Resources:
Abstract
1214 - Neo-adjuvant (NA) Imatinib for gastrointestinal stromal tumours (GISTs): What is the optimal length of treatment?
Presenter: Tom Wilson
Session: Poster Display session 1
Resources:
Abstract
2690 - Gastrointestinal Stromal Tumours (GIST) in adolescents and young adults (AYA)
Presenter: Nikki Ijzerman
Session: Poster Display session 1
Resources:
Abstract
4558 - Radiomics improves response evaluation for desmoid tumors treated with chemotherapy
Presenter: Amandine Crombe
Session: Poster Display session 1
Resources:
Abstract
2751 - Radiomics of gastrointestinal stromal tumors; risk classification based on computed tomography images – a pilot study
Presenter: Milea Timbergen
Session: Poster Display session 1
Resources:
Abstract
2737 - Differentiating well-differentiated liposarcomas from lipomas using a radiomics approach
Presenter: Melissa Vos
Session: Poster Display session 1
Resources:
Abstract
1282 - The immune landscape of chondrosarcoma reveals an anti inflammatory environment
Presenter: Iseulys Richert
Session: Poster Display session 1
Resources:
Abstract
1572 - Impact of Immunotherapy and Targeted Therapy on Tumor Growth Rate in Sarcoma
Presenter: Esmail Al-ezzi
Session: Poster Display session 1
Resources:
Abstract
3414 - DNA methylation profiles of angiosarcoma subtypes.
Presenter: Marije Weidema
Session: Poster Display session 1
Resources:
Abstract
3411 - Prognostic significance of circulating PD-1, PD-L1, pan-BTN3As and BTN3A1 in patients with metastatic gastrointestinal stromal tumors (mGISTs)
Presenter: Daniele Fanale
Session: Poster Display session 1
Resources:
Abstract