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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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15d-PGJ2 inhibits NF-κB and AP-1-mediated MMP-9 expression and invasion of breast cancer cell by means of a heme oxygenase-1-dependent mechanism

  • Jang, Hye-Yeon (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School) ;
  • Hong, On-Yu (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School) ;
  • Youn, Hyun Jo (Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University and Biomedical Research Institute) ;
  • Kim, Min-Gul (Department of Pharmacology, Institute for Medical Sciences, Chonbuk National University Medical School) ;
  • Kim, Cheorl-Ho (Molecular and Cellular Glycobiology Unit, Department of Biological Sciences, Sung Kyun Kwan University) ;
  • Jung, Sung Hoo (Department of Surgery, Research Institute of Clinical Medicine, Chonbuk National University Hospital, Chonbuk National University and Biomedical Research Institute) ;
  • Kim, Jong-Suk (Department of Biochemistry, Institute for Medical Sciences, Chonbuk National University Medical School)
  • Received : 2019.06.17
  • Accepted : 2019.09.24
  • Published : 2020.04.30
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Abstract

Activation of peroxisome proliferator-activated receptor γ (PPARγ) serves as a key factor in the proliferation and invasion of breast cancer cells and is a potential therapeutic target for breast cancer. However, the mechanisms underlying this effect remain largely unknown. Heme oxygenase-1 (HO-1) is induced and over-expressed in various cancers and is associated with features of tumor aggressiveness. Recent studies have shown that HO-1 is a major downstream target of PPARγ. In this study, we investigated the effects of induction of HO-1 by PPARγ on TPA-induced MMP-9 expression and cell invasion using MCF-7 breast cancer cells. TPA treatment increased NF-κB /AP-1 DNA binding as well as MMP-9 expression. These effects were significantly blocked by 15d-PGJ2, a natural PPARγ ligand. 15d-PGJ2 induced HO-1 expression in a dose-dependent manner. Interestingly, HO-1 siRNA significantly attenuated the inhibition of TPA-induced MMP-9 protein expression and cell invasion by 15d-PGJ2. These results suggest that 15d-PGJ2 inhibits TPA-induced MMP-9 expression and invasion of MCF-7 cells by means of a heme oxygenase-1-dependent mechanism. Therefore, PPARγ/HO-1 signaling-pathway inhibition may be beneficial for prevention and treatment of breast cancer.

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References

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