title: Inactivation of Ets 1 transcription factor by a specific decoy strategy reduces rat C6 glioma cell proliferation and mmp-9 expression.
abstract: 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.
authors.affiliation: Institute of Pathology, University of Bonn, 53011 Bonn, Germany.
authors.forename: Ayguen
authors.initials: A
authors.lastname: Sahin
authors.forename: Markus
authors.initials: M
authors.lastname: Velten
authors.forename: Torsten
authors.initials: T
authors.lastname: Pietsch
authors.forename: Pascal
authors.initials: P
authors.lastname: Knuefermann
authors.forename: Ali Fuat
authors.initials: AF
authors.lastname: Okuducu
authors.forename: Jens Claus
authors.initials: JC
authors.lastname: Hahne
authors.forename: Nicolas
authors.initials: N
authors.lastname: Wernert
mesh_terms: 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
chemical_list: 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