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

Research output: Contribution to journalArticle

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

Fingerprint

Androgen Receptors
prostatic neoplasms
androgens
Androgens
Canidae
Prostatic Neoplasms
cell lines
Cell Line
dogs
dimerization
Dimerization
androgen receptors
neoplasm cells
assays
Glutamine
glutamine
Animal Models
animal models
neoplasms

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

Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines. / Kato, Yuiko; Ochiai, Kazuhiko; Kawakami, Shota; Nakao, Nobuhiro; Azakami, Daigo; Bonkobara, Makoto; Michishita, Masaki; Morimatsu, Masami; Watanabe, Masami; Omi, Toshinori.

In: BMC Veterinary Research, Vol. 13, No. 1, 170, 09.06.2017.

Research output: Contribution to journalArticle

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, vol. 13, no. 1, 170. https://doi.org/10.1186/s12917-017-1094-4
Kato, Yuiko ; Ochiai, Kazuhiko ; Kawakami, Shota ; Nakao, Nobuhiro ; Azakami, Daigo ; Bonkobara, Makoto ; Michishita, Masaki ; Morimatsu, Masami ; Watanabe, Masami ; Omi, Toshinori. / Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines. In: BMC Veterinary Research. 2017 ; Vol. 13, No. 1.
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AU - Nakao, Nobuhiro

AU - Azakami, Daigo

AU - Bonkobara, Makoto

AU - Michishita, Masaki

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AU - Omi, Toshinori

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AB - 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.

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