Inactivation of Ets 1 transcription factor by a specific decoy strategy reduces rat C6 glioma cell proliferation and mmp-9 expression.
Malignant gliomas represent the most aggressive tumours of the central nervous system and are characterised by both extensive proliferation and invasive growth. Matrix degrading proteases called matrix metalloproteinases (MMPs), particularly MMP-9, play a crucial role in glioma infiltration. The activity of these enzymes is regulated at different levels. In this regard, the control of transcriptional activity by specific transcription factors is believed to be very important. In the present study, we examined whether rat C6 glioma cells express the Ets 1 transcription factor and whether inhibition of Ets 1 by a specific decoy strategy affects C6 glioma cell proliferation and mmp-9 expression. We found that C6 glioma cells express Ets 1 and can efficiently be transfected with an Ets 1-specific decoy oligodesoxynucleotide (ODN). This ODN significantly reduces cell proliferation and mmp-9 expression, the latter in a dose-dependent manner. We conclude that inhibition of transcription factors, which play a role for glioma development and progression such as Ets 1 by specific decoy approaches, might represent useful tools for experimental therapeutic strategies against malignant gliomas.
Sahin
Ayguen
A
Institute of Pathology, University of Bonn, 53011 Bonn, Germany.
Velten
Markus
M
Pietsch
Torsten
T
Knuefermann
Pascal
P
Okuducu
Ali Fuat
AF
Hahne
Jens Claus
JC
Wernert
Nicolas
N
D000818:Animals; D049109:Cell Proliferation; D015536:Down-Regulation; D005910:Glioma; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis*; D009841:Oligonucleotides / Q000494:pharmacology; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D050783:Proto-Oncogene Proteins c-ets; D051381:Rats; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
C494043:Ets1 protein, rat; D009841:Oligonucleotides; D050784:Proto-Oncogene Protein c-ets-1; D011518:Proto-Oncogene Proteins; D050783:Proto-Oncogene Proteins c-ets; D014157:Transcription Factors; D020780:Matrix Metalloproteinase 9