| Autor: |
Attila Varga, Tibor Vántus, M.T. Nguyen, B. Bátai, Pál Gyulavári, C. Sőti |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
Annals of Oncology. 30:v806 |
| ISSN: |
0923-7534 |
| DOI: |
10.1093/annonc/mdz269.030 |
| Popis: |
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. 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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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