BMB Reports

Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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G protein-coupled estrogen receptor-1 agonist induces chemotherapeutic effect via ER stress signaling in gastric cancer

  • Lee, Seon-Jin (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Tae Woo (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Park, Gyeong Lim (Environmental Disease Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Hwang, Yo Sep (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Cho, Hee Jun (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Kim, Jong-Tae (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology) ;
  • Lee, Hee Gu (Immunotherapy Convergence Research Center, Korea Research Institute of Bioscience and Biotechnology)
  • Received : 2019.01.05
  • Accepted : 2019.04.08
  • Published : 2019.11.30
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Abstract

G protein-coupled estrogen receptor (GPER) is known to play an important role in hormone-associated cancers. G-1, a novel synthetic GPER agonist, has been reported to exhibit anti-carcinogenic properties. However, the chemotherapeutic mechanism of GPER is yet unclear. Here, we evaluated GPER expression in human gastric cancer tissues and cells. We found that G-1 treatment attenuates GPER expression in gastric cancer. GPER expression increased G-1-induced antitumor effects in mouse xenograft model. We analyzed the effects of knockdown/overexpression of GPER on G-1-induced cell death in cancer cells. Increased GPER expression in human gastric cancer cells increased G-1-induced cell death via increased levels of cleaved caspase-3, -9, and cleaved poly ADP-ribose polymerase. Interestingly, during G-1-induced cell death, GPER mRNA and protein expression was attenuated and associated with ER stress-induced expression of PERK, ATF-4, GRP-78, and CHOP. Furthermore, PERK-dependent induction of ER stress activation increased G-1-induced cell death, whereas PERK silencing decreased cell death and increased drug sensitivity. Taken together, the data suggest that the induction of ER stress via GPER expression may increase G-1-induced cell death in gastric cancer cells. These results may contribute to a new paradigm shift in gastric cancer therapy.

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References

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