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Journal of Cancer Research and Clinical Oncology

, Volume 145, Issue 9, pp 2293–2301 | Cite as

Dihydrotestosterone promotes kidney cancer cell proliferation by activating the STAT5 pathway via androgen and glucocorticoid receptors

  • Sahyun Pak
  • Wansuk Kim
  • Yunlim Kim
  • Cheryn Song
  • Hanjong AhnEmail author
Original Article – Cancer Research
  • 111 Downloads

Abstract

Purpose

Androgen receptors (ARs) are expressed on a variety of cell types, and AR signaling plays an important role in tumor development and progression in several cancers. This in vitro study evaluated the effect of dihydrotestosterone (DHT) on the proliferation of renal cell carcinoma (RCC) cells in relation to AR status.

Methods

Steroid hormone receptor expression was evaluated using RT-PCR and Western blotting. The effect of DHT on cell proliferation and STAT5 phosphorylation was evaluated in RCC cell lines (Caki-2, A498, and SN12C) and primary RCC cells using cell viability assays and Western blotting. ARs and glucocorticoid receptors (GRs) were knocked down with small interfering RNAs before assessing changes in cell proliferation and STAT5 activation.

Results

DHT treatment promoted cell proliferation and increased STAT5 phosphorylation regardless of AR status. The AR antagonist bicalutamide reduced kidney cancer cell proliferation, regardless of AR status. AR and GR knockdown blocked STAT5 activation and reduced cell proliferation in all RCC cell lines. In patient-derived primary cells, DHT enhanced cell proliferation and this effect was diminished by treatment with the AR antagonists bicalutamide and enzalutamide and the GR antagonist mifepristone.

Conclusion

DHT promotes cell proliferation through STAT5 activation in RCC cells, regardless of AR status. DHT appears to utilize the AR and GR pathways to activate STAT5, and the inhibition of AR and GR showed antitumor activity in RCC cells. These data suggest that targeting AR and GR may be a promising new approach to the treatment of RCC.

Keywords

Kidney neoplasms Androgen receptor Glucocorticoid receptor STAT5 transcription factor 

Notes

Acknowledgements

This study was supported by a Grant (W2014-012) from the Asan Institute for Life Sciences, Asan Medical Center, Seoul, Korea.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

Supplementary material

432_2019_2993_MOESM1_ESM.docx (1011 kb)
Supplementary material 1 (DOCX 1010 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Urology, Center for Urologic CancerNational Cancer CenterGoyangKorea
  2. 2.Department of UrologyInje University Busan Paik HospitalBusanKorea
  3. 3.Asan Institute for Life ScienceAsan Medical CenterSeoulKorea
  4. 4.Department of UrologyAsan Medical Center, University of Ulsan College of MedicineSeoulKorea

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