Gamma-Irradiation enhances RECK protein levels in Panc-1 pancreatic canter cells

Na Young Kim, Jung Eun Lee, Hye Jin Chang, Chae Seung Lim, Deok Hwa Nam, Bon Hong Min, Gil Hong Park, Jun Seo Oh

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 NMP 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)-β1 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-β receptor I kinase, abolished TGF-β1- 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-β signaling, and that irradiation increases Panc-1 invasiveness via a mechanism that may not be linked to MMP-2 activity.

Original languageEnglish
Pages (from-to)105-111
Number of pages7
JournalMolecules and cells
Volume25
Issue number1
Publication statusPublished - 2008 Feb 29

Keywords

  • Extracellular matrix
  • RECK
  • Radiation
  • TGF-β
  • TIMP

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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