Overexpression of ICBP90, a novel CCAAT-binding protein, overcomes cell contact inhibition by forcing topoisomerase II alpha expression.
We have recently identified ICBP90 as being a protein able to bind in vitro a CCAAT box of the topoisomerase II alpha gene promoter. The aim of the present work was to check whether ICBP90 is able to regulate in vivo topoisomerase II alpha expression in human lung fibroblasts under various proliferating conditions. Transient transfection experiments performed on moderately growing human lung fibroblasts (50% of confluence) showed that overexpression of ICBP90 is associated with an elevation of topoisomerase II alpha expression and an increase of the cell proliferation rate. In highly proliferating human lung fibroblasts (20% confluence) overexpression of ICBP90 had no effect. In contrast, in non-proliferating fibroblasts (100% confluence) overexpression of ICBP90 allowed recovery of topoisomerase II alpha expression levels with a concomitant overgrowth of confluent cell cultures. Our results show that ICBP90 regulates topoisomerase II alpha expression and is able to overcome cell contact inhibition signaling, suggesting that increased ICBP90 expression may be involved in carcinogenesis.
Hopfner
Raphael
R
Institut National de la Santé et de la Recherche Médicale U425, Faculté de Pharmacie, 74 route du Rhin, B.P. 24, 67401 Illkirch, France.
Mousli
Marc
M
Oudet
Pierre
P
Bronner
Christian
C
D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000235:genetics / Q000502:physiology; D002478:Cells, Cultured; D003260:Contact Inhibition / Q000235:genetics / Q000502:physiology*; D004250:DNA Topoisomerases, Type II / Q000096:biosynthesis* / Q000235:genetics; D004268:DNA-Binding Proteins; D004790:Enzyme Induction; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology; D006367:HeLa Cells; D006801:Humans; D008168:Lung / Q000166:cytology / Q000201:enzymology / Q000502:physiology; D010957:Plasmids / Q000235:genetics; D011401:Promoter Regions, Genetic; D014162:Transfection / Q000379:methods; D044767:Ubiquitin-Protein Ligases
D000951:Antigens, Neoplasm; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; C406364:UHRF1 protein, human; D044767:Ubiquitin-Protein Ligases; D004250:DNA Topoisomerases, Type II