Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer

Yuiko Kato, Kazuhiko Ochiai, Masaki Michishita, Daigo Azakami, Rei Nakahira, Masami Morimatsu, Toshina Ishiguro-Oonuma, Yasunaga Yoshikawa, Masato Kobayashi, Makoto Bonkobara, Masanori Kobayashi, Kimimasa Takahashi, Masami Watanabe, Toshinori Omi

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Although the morbidity of canine prostate cancer is low, the majority of cases present with resistance to androgen therapy and poor clinical outcomes. These pathological conditions are similar to the signs of the terminal stage of human androgen-independent prostate cancer. The co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) is known to be overexpressed in human androgen-independent prostate cancer. However, there is little information about the structure and function of canine SGTA. In this study, canine SGTA was cloned and analysed for its ability to suppress androgen receptor signalling.The full-length open reading frame (ORF) of the canine SGTA gene was amplified by RT-PCR using primers designed from canine-expressed sequence tags that were homologous to human SGTA. The canine SGTA ORF has high homology with the corresponding human (89%) and mouse (81%) sequences. SGTA dimerisation region and tetratricopeptide repeat (TPR) domains are conserved across the three species. The ability of canine SGTA to undergo homodimerisation was demonstrated by a mammalian two-hybrid system and a pull-down assay. The negative impact of canine SGTA on androgen receptor (AR) signalling was demonstrated using a reporter assay in androgen-independent human prostate cancer cell lines. Pathological analysis showed overexpression of SGTA in canine prostate cancer, but not in hyperplasia. A reporter assay in prostate cells demonstrated suppression of AR signalling by canine SGTA. Altogether, these results suggest that canine SGTA may play an important role in the acquisition of androgen independence by canine prostate cancer cells.

Original languageEnglish
Pages (from-to)143-148
Number of pages6
JournalVeterinary Journal
Volume206
Issue number2
DOIs
Publication statusPublished - Nov 2015

Keywords

  • Androgen receptor
  • Cancer
  • Canine
  • Prostate
  • SGTA

ASJC Scopus subject areas

  • Animal Science and Zoology
  • veterinary(all)

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    Kato, Y., Ochiai, K., Michishita, M., Azakami, D., Nakahira, R., Morimatsu, M., Ishiguro-Oonuma, T., Yoshikawa, Y., Kobayashi, M., Bonkobara, M., Kobayashi, M., Takahashi, K., Watanabe, M., & Omi, T. (2015). Molecular cloning of canine co-chaperone small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA) and investigation of its ability to suppress androgen receptor signalling in androgen-independent prostate cancer. Veterinary Journal, 206(2), 143-148. https://doi.org/10.1016/j.tvjl.2015.08.002