Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines

Yuiko Kato, Kazuhiko Ochiai, Shota Kawakami, Nobuhiro Nakao, Daigo Azakami, Makoto Bonkobara, Masaki Michishita, Masami Morimatsu, Masami Watanabe, Toshinori Omi

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3 Citations (Scopus)

Abstract

Background: The pathological condition of canine prostate cancer resembles that of human androgen-independent prostate cancer. Both canine and human androgen receptor (AR) signalling are inhibited by overexpression of the dimerized co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), which is considered to cause the development of androgen-independency. Reduced expression in immortalised cells (REIC/Dkk-3) interferes with SGTA dimerization and rescues AR signalling. This study aimed to assess the effects of REIC/Dkk-3 and SGTA interactions on AR signalling in the canine androgen-independent prostate cancer cell line CHP-1. Results: Mammalian two-hybrid and Halo-tagged pull-down assays showed that canine REIC/Dkk-3 interacted with SGTA and interfered with SGTA dimerization. Additionally, reporter assays revealed that canine REIC/Dkk-3 restored AR signalling in both human and canine androgen-independent prostate cancer cells. Therefore, we confirmed the interaction between canine SGTA and REIC/Dkk-3, as well as their role in AR signalling. Conclusions: Our results suggest that this interaction might contribute to the development of a novel strategy for androgen-independent prostate cancer treatment. Moreover, we established the canine androgen-independent prostate cancer model as a suitable animal model for the study of this type of treatment-refractory human cancer.

Original languageEnglish
Article number170
JournalBMC Veterinary Research
Volume13
Issue number1
DOIs
Publication statusPublished - Jun 9 2017

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Keywords

  • Androgen receptor (AR) signalling
  • Canine
  • Prostate cancer
  • Reduced expression in immortalised cells (REIC/Dkk-3)
  • Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA)

ASJC Scopus subject areas

  • veterinary(all)

Cite this

Kato, Y., Ochiai, K., Kawakami, S., Nakao, N., Azakami, D., Bonkobara, M., Michishita, M., Morimatsu, M., Watanabe, M., & Omi, T. (2017). Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines. BMC Veterinary Research, 13(1), [170]. https://doi.org/10.1186/s12917-017-1094-4