TY - JOUR
T1 - Canine REIC/Dkk-3 interacts with SGTA and restores androgen receptor signalling in androgen-independent prostate cancer cell lines
AU - Kato, Yuiko
AU - Ochiai, Kazuhiko
AU - Kawakami, Shota
AU - Nakao, Nobuhiro
AU - Azakami, Daigo
AU - Bonkobara, Makoto
AU - Michishita, Masaki
AU - Morimatsu, Masami
AU - Watanabe, Masami
AU - Omi, Toshinori
N1 - Funding Information:
This work supported by KAKENHI scientific research grants from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 15 K07754).
Publisher Copyright:
© 2017 The Author(s).
PY - 2017/6/9
Y1 - 2017/6/9
N2 - 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.
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.
KW - Androgen receptor (AR) signalling
KW - Canine
KW - Prostate cancer
KW - Reduced expression in immortalised cells (REIC/Dkk-3)
KW - Small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA)
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U2 - 10.1186/s12917-017-1094-4
DO - 10.1186/s12917-017-1094-4
M3 - Article
C2 - 28599655
AN - SCOPUS:85020377871
SN - 1746-6148
VL - 13
JO - BMC Veterinary Research
JF - BMC Veterinary Research
IS - 1
M1 - 170
ER -
