Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53

Maarten Niemantsverdriet; Edwin de Jong; Johannes A Langendijk; Harm H Kampinga; Robert P Coppes

doi:10.1016/j.radonc.2010.04.002

Synergistic induction of profibrotic PAI-1 by TGF-β and radiation depends on p53

Radiother Oncol. 2010 Oct;97(1):33-5. doi: 10.1016/j.radonc.2010.04.002.

Authors

Maarten Niemantsverdriet¹, Edwin de Jong, Johannes A Langendijk, Harm H Kampinga, Robert P Coppes

Affiliation

¹ Department of Cell Biology, University Medical Center Groningen, University of Groningen, The Netherlands.

PMID: 20435362
DOI: 10.1016/j.radonc.2010.04.002

Abstract

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.

MeSH terms

Cell Line, Tumor
Dose-Response Relationship, Radiation
Fibrosis / etiology
Fibrosis / genetics
Gene Expression / genetics
Gene Expression / radiation effects
HeLa Cells
Humans
Immunoblotting
Neoplasms / genetics*
Neoplasms / radiotherapy*
Phosphorylation
Plasminogen Activator Inhibitor 1 / genetics*
Radiation Tolerance / genetics*
Radiotherapy / adverse effects*
Reverse Transcriptase Polymerase Chain Reaction
Transcriptional Activation / genetics
Transcriptional Activation / radiation effects
Transforming Growth Factor beta1 / genetics*
Tumor Suppressor Protein p53 / genetics*

Substances

Plasminogen Activator Inhibitor 1
TGFB1 protein, human
Transforming Growth Factor beta1
Tumor Suppressor Protein p53