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Poster Display session 1

3309 - Heat Shock Protein 90 chaperones and Protein Kinase D3 regulates androgen-independent prostate cancer development

Date

28 Sep 2019

Session

Poster Display session 1

Topics

Pathology/Molecular Biology

Tumour Site

Prostate Cancer

Presenters

Attila Varga

Citation

Annals of Oncology (2019) 30 (suppl_5): v797-v815. 10.1093/annonc/mdz269

Authors

A. Varga1, B. Bátai2, P. Gyulavári1, M.T. Nguyen3, C. Sőti3, T. Vántus3

Author affiliations

  • 1 Mta Se Pathobiochemistry Research Group, Semmelweis University, 1094 - Budapest/HU
  • 2 Mta-se Momentum Molecular Oncohematology Research Group, 1st Department Of Pathology And Experimental Cancer Research, Semmelweis University, 1085 - Budapest/HU
  • 3 Department Of Medical Chemistry, Molecular Biology And Pathobiochemistry, Semmelweis University, 1094 - Budapest/HU

Resources

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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.

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