論文

査読有り 国際誌
2020年8月

Tumor suppressor REIC/Dkk-3 and its interacting protein SGTA inhibit glucocorticoid receptor to nuclear transport.

Experimental and therapeutic medicine
  • Takehiro Iwata
  • ,
  • Takuya Sadahira
  • ,
  • Kazuhiko Ochiai
  • ,
  • Hideo Ueki
  • ,
  • Takanori Sasaki
  • ,
  • Peng Haung
  • ,
  • Motoo Araki
  • ,
  • Toyohiko Watanabe
  • ,
  • Yasutomo Nasu
  • ,
  • Masami Watanabe

20
2
開始ページ
1739
終了ページ
1745
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.3892/etm.2020.8819
出版者・発行元
Spandidos Publications

REIC/Dkk-3 is a tumor suppressor, and its expression is significantly downregulated in a variety of human cancer types. A previous study performed yeast two-hybrid screening and identified the small glutamine-rich tetratricopeptide repeat-containing protein α (SGTA), known as a negative modulator of cytoplasmic androgen receptor (AR) signaling, which is a novel interacting partner of REIC/Dkk-3. The previous study also indicated that the REIC/Dkk-3 protein interferes with the dimerization of SGTA and then upregulates the AR transport and signaling in human prostate cancer PC3 cells. Since the transport of some steroid receptors to nucleus is conducted similarly by dynein motor-dependent way, the current study aimed to investigate the role of SGTA and REIC/Dkk-3 in the transport of other glucocorticoid receptors (GR). In vitro reporter assays for the cytoplasmic GR transport were performed in human prostate cancer PC3 cells and 293T cells. As for the SGTA protein, a suppressive effect on the GR transport to the nucleus was observed in the cells. As for the REIC/Dkk-3 protein, an inhibitory effect was observed for the GR transport in PC3 cells. Under the depleted condition of SGTA by short-hairpin (sh)RNA, the downregulation of GR transport by REIC/Dkk-3 was significantly enhanced compared with the non-depleted condition in PC3 cells, suggesting a compensatory role of REIC/Dkk-3 in the SGTA mediated inhibition of GR transport. The current study therefore demonstrated that SGTA inhibited the cytoplasmic transport of GR in 293T and PC3 cells, and REIC/Dkk-3 also inhibited the cytoplasmic transport of GR in PC3 cells. These results may be used to gain novel insight into the GR transport and signaling in normal and cancer cells.

リンク情報
DOI
https://doi.org/10.3892/etm.2020.8819
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/32765682
PubMed Central
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7388570
ID情報
  • DOI : 10.3892/etm.2020.8819
  • ISSN : 1792-0981
  • eISSN : 1792-1015
  • PubMed ID : 32765682
  • PubMed Central 記事ID : PMC7388570

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