Gamma-irradiation enhances RECK protein levels in Panc-1 pancreatic cancer cells.
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)-Beta1 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-Beta1- 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.
Kim
Na Young
NY
Laboratory of Cellular Oncology, Korea University Graduate School of Medicine, Ansan 425-707, Korea.
Lee
Jung Eun
JE
Chang
Hyeu Jin
HJ
Lim
Chae Seung
CS
Nam
Deok Hwa
DH
Min
Bon Hong
BH
Park
Gil Hong
GH
Oh
Jun Seo
JS
D001549:Benzamides / Q000378:metabolism; D045744:Cell Line, Tumor / Q000378:metabolism / Q000528:radiation effects; D004149:Dioxoles / Q000378:metabolism; D058851:GPI-Linked Proteins; D005720:Gamma Rays; D020869:Gene Expression Profiling; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000378:metabolism / Q000532:radiotherapy; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D015398:Signal Transduction / Q000502:physiology; D051906:Smad7 Protein / Q000235:genetics / Q000378:metabolism; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
C459179:4-(5-benzo(1,3)dioxol-5-yl-4-pyridin-2-yl-1H-imidazol-2-yl)benzamide; D001549:Benzamides; D004149:Dioxoles; D058851:GPI-Linked Proteins; D008562:Membrane Glycoproteins; C115460:RECK protein, human; D018125:Receptors, Transforming Growth Factor beta; D051906:Smad7 Protein; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2