Dominant-negative inhibition of Ets 1 suppresses tumor growth, invasion and migration in rat C6 glioma cells and reveals differentially expressed Ets 1 target genes.
We previously reported that the inactivation of the Ets 1 transcription factor by a specific decoy strategy reduces rat C6 glioma cell proliferation and mmp-9 expression. In the present study, we analysed the effects of the dominant-negative form of Ets 1 (Ets-DB) on rat C6 glioma cell proliferation, migration, invasion, in vivo tumor growth on the chicken chorioallantoic membrane (CAM) and mmp-9 expression. In addition, we examined differences in gene expression between Ets-DB expressing and control cells using suppression subtractive hybridization (SSH). We found that retrovirus mediated expression of Ets-DB inhibited cellular proliferation, migration, invasion, mmp-9 expression, cellular growth in soft agar, and in vivo growth in the chicken chorioallantoic membrane assay. SSH analysis revealed expression of different genes in Ets-DB expressing cells involved in basic cellular processes. Each of these genes contained binding sites for different Ets-factors within their promoters. Finally, we found that, in addition to Ets 1, Elk-1, Elf-1, Fli-1 and Etv-1 are further Ets family members expressed in rat C6 glioma cells. Our results indicate that Ets transcription factors play important roles for basic properties of rat C6 glioma cells. Targeting of these factors might therefore become a useful experimental tool for therapeutic strategies against malignant gliomas.
Sahin
Ayguen
A
Institute of Pathology, Department of Neuropathology, University of Bonn, 53011 Bonn, Germany.
Vercamer
Chantal
C
Kaminski
Annette
A
Fuchs
Tanja
T
Florin
Alexandra
A
Hahne
Jens Claus
JC
Mattot
Virginie
V
Pourtier-Manzanedo
Albin
A
Pietsch
Torsten
T
Fafeur
Véronique
V
Wernert
Nicolas
N
D000482:Allantois; D000818:Animals; D001665:Binding Sites; D002455:Cell Division; D045744:Cell Line, Tumor; D002642:Chick Embryo; D002823:Chorion; D017931:DNA Primers; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics; D050784:Proto-Oncogene Protein c-ets-1 / Q000037:antagonists & inhibitors* / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D009363:Neoplasm Proteins; D050784:Proto-Oncogene Protein c-ets-1; D020780:Matrix Metalloproteinase 9