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Transglutaminase-2 Is Involved in All-Trans Retinoic Acid-Induced Invasion and Matrix Metalloproteinases Expression of SH-SY5Y Neuroblastoma Cells via NF-κB Pathway

  • Lee, Hye-Ja (College of Pharmacy, Dongguk University) ;
  • Park, Mi-Kyung (College of Pharmacy, Dongguk University) ;
  • Bae, Hyun-Cheol (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Yoon, Hee-Jung (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Kim, Soo-Youl (Division of Cancer Biology, Research Institute, National Cancer Center) ;
  • Lee, Chang-Hoon (College of Pharmacy, Dongguk University)
  • Received : 2012.02.06
  • Accepted : 2012.05.03
  • Published : 2012.05.31

Abstract

All-trans retinoic acid (ATRA) is currently used in adjuvant differentiation-based treatment of residual or relapsed neuroblastoma (NB). It has been reported that short-term ATRA treatment induces migration and invasion of SH-SY5Y via transglutaminase-2 (Tgase-2). However, the detailed mechanism of Tgase-2's involvement in NB cell invasion remains unclear. Therefore we investigated the role of Tgase-2 in invasion of NB cells using SH-SY5Y cells. ATRA dose-dependently induced the invasion of SH-SY5Y cells. Cystamine (CTM), a well known tgase inhibitor suppressed the ATRA-induced invasion of SH-SY5Y cells in a dose-dependent manner. Matrix metalloproteinase -9 (MMP-9) and MMP-2, well known genes involved in invasion of cancer cells were induced in the ATRA-induced invasion of the SH-SH5Y cells. Treatment of CTM suppressed the MMP-9 and MMP-2 enzyme activities in the ATRA-induced invasion of the SH-SY5Y cells. To confirm the involvement of Tgase-2, gene silencing of Tgase-2 was performed in the ATRA-induced invasion of the SH-SH5Y cells. The siRNA of Tgase-2 suppressed the MMP-9 and MMP-2 activity of the SH-SY5Y cells. MMP-2 and MMP-9 are well known target genes of NF-${\kappa}B$. Therefore the relationship of Tgase-2 and NF-${\kappa}B$ in the ATRA-induced invasion of the SH-SY5Y cells was examined using siRNA and CTM. ATRA induced the activation of NF-${\kappa}B$ in the SH-SY5Y cells and CTM suppressed the activation of NF-${\kappa}B$. Gene silencing of Tgase-2 suppressed the MMP expression by ATRA. These results suggested that Tgase-2 might be a new target for controlling the ATRA-induced invasion of NBs.

Keywords

References

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