Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53.
Radiation-induced fibrosis is a severe side effect of radiotherapy. TGF-β and radiation synergistically induce expression of the profibrotic PAI-1 gene and this cooperation potentially involves p53. Here, we demonstrate that p53 is both indispensable and sufficient for the radiation effect inducing synergistic activation of PAI-1 by radiation and TGF-β.
Niemantsverdriet
Maarten
M
Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands.
de Jong
Edwin
E
Langendijk
Johannes A
JA
Kampinga
Harm H
HH
Coppes
Robert P
RP
D045744:Cell Line, Tumor; D004307:Dose-Response Relationship, Radiation; D005355:Fibrosis / Q000209:etiology / Q000235:genetics; D015870:Gene Expression / Q000235:genetics / Q000528:radiation effects; D006367:HeLa Cells; D006801:Humans; D015151:Immunoblotting; D009369:Neoplasms / Q000235:genetics* / Q000532:radiotherapy*; D010766:Phosphorylation; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D011878:Radiotherapy / Q000009:adverse effects*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015533:Transcriptional Activation / Q000235:genetics / Q000528:radiation effects; D053773:Transforming Growth Factor beta1 / Q000235:genetics*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
D017395:Plasminogen Activator Inhibitor 1; C508960:TGFB1 protein, human; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53