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
920 - Efficacy of intravenous (IV) NEPA, a fixed NK1/5-HT3 receptor antagonist (RA) combination, for prevention of CINV following cisplatin- and anthracycline cyclophosphamide (AC)-based chemotherapy (CT)
Presenter: Lee Schwartzberg
Session: Poster Display session 1
Resources:
Abstract
5146 - Efficacy of olanzapine combination in prevention of nausea & vomiting in highly emetogenic chemotherapy
Presenter: Smitha Saldanha
Session: Poster Display session 1
Resources:
Abstract
1947 - Patient-reported outcome data during real-world use of NEPA for prevention of chemotherapy-induced nausea and vomiting in high-risk platin-receiving patients - A prospective multicenter trial
Presenter: Meinolf Karthaus
Session: Poster Display session 1
Resources:
Abstract
6163 - A study evaluating steroid induced metabolic syndrome after antiemetic dexamethasone therapy in patients received high emetic risk chemotherapy
Presenter: Hee Jun Kim
Session: Poster Display session 1
Resources:
Abstract
2154 - High incidence of nausea during initial and repeated courses if intravenous chemotherapy in patients receiving guideline consistent antiemetic prophylaxis - a prospective, observational, real world study.
Presenter: Teresa Smit
Session: Poster Display session 1
Resources:
Abstract
1637 - "Randomised controlled trial of Scalp Cooling (SC) for the prevention of Chemotherapy Induced Alopecia (CIA)”
Presenter: Jyoti Bajpai
Session: Poster Display session 1
Resources:
Abstract
5351 - Performance of the ‘4S rule’ to predict short-term outcomes in cancer outpatients with unsuspected pulmonary embolism.
Presenter: David Pesántez Coronel
Session: Poster Display session 1
Resources:
Abstract
1189 - Prevalence of venous thromboembolism based on intensive screening for patients with advanced solid tumor in prospective observational study
Presenter: Shota Omori
Session: Poster Display session 1
Resources:
Abstract
4340 - Short-term outcomes of cancer patients with pulmonary embolism according to the setting (hospital-acquired vs. outpatient) at diagnosis.
Presenter: Diego Muñoz Guglielmetti
Session: Poster Display session 1
Resources:
Abstract
4658 - Patient-reported outcomes associated with switching to rivaroxaban for the treatment of venous thromboembolism (VTE) in patients with active cancer
Presenter: Alexander Cohen
Session: Poster Display session 1
Resources:
Abstract