Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Gamma-Irradiation Enhances RECK Protein Levels in Panc-1 Pancreatic Cancer Cells

  • Kim, Na Young (Laboratory of Cellular Oncology, Korea University Graduate School of Medicine) ;
  • Lee, Jung Eun (Laboratory of Cellular Oncology, Korea University Graduate School of Medicine) ;
  • Chang, Hyeu Jin (Laboratory of Cellular Oncology, Korea University Graduate School of Medicine) ;
  • Lim, Chae Seung (Department of Laboratory Medicine, Korea University Graduate School of Medicine) ;
  • Nam, Deok Hwa (Department of Laboratory Medicine, Korea University Graduate School of Medicine) ;
  • Min, Bon Hong (Department of Pharmacology, Korea University Graduate School of Medicine) ;
  • Park, Gil Hong (Department of Biochemistry, Korea University Graduate School of Medicine) ;
  • Oh, Jun Seo (Laboratory of Cellular Oncology, Korea University Graduate School of Medicine)
  • Received : 2007.07.30
  • Accepted : 2007.10.09
  • Published : 2008.02.29
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Abstract

Radiotherapy is an important treatment for many malignant tumors, but there are recent reports that radiation may increase the malignancy of cancer cells by stimulating expression of type IV collagenases. In this study, we examined changes in matrix metalloproteinase (MMP) inhibitors, such as the tissue inhibitors of metalloproteinase (TIMP)-1, TIMP-2 and RECK, in response to irradiation in Panc-1 pancreatic cancer cells. Irradiation increased RECK protein levels but not mRNA levels, whereas no significant changes were found in TIMP-1 and TIMP-2. The enhanced RECK protein levels were associated with an increase in MMP inhibitory activity. However, irradiation slightly but reproducibly increased the invasiveness of the Panc-1 cells. Like irradiation, treatment of Panc-1 cells with transforming growth factor $(TGF)-{\beta}1$ led to a 2-fold increase in RECK protein levels. Transient transfection with Smad3 also increased RECK protein levels, but transfection with Smad7 markedly reduced them. Stable expression of Smad7 and treatment with SB431542, an inhibitor of $TGF-{\beta}$ receptor I kinase, abolished $TGF-{\beta}1$- and radiation-mediated effects on RECK. Furthermore, irradiation increased levels of phosphorylated Smad3. We conclude that radiation post-transciptionally enhances RECK protein levels in Panc-1 cells, at least in part, via $TGF-{\beta}$ signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.

Keywords

Acknowledgement

Supported by : Ministry of Science and Technology

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