Identification of CBFA1-regulated genes on SaOs-2 cells.
Current knowledge about mechanisms controlling osteoblast-specific gene expression has led to the identification of Cbfa1 as a key regulator of osteoblast differentiation. Several essential questions about this transcription factor remain to be addressed, e.g., the nature of stimuli that may modulate its own expression, as well as the genetic repercussions following alterations in Cbfa1 levels. To identify such Cbfa1-responsive genes, the SaOs-2 cell line was stably transfected with a dominant negative mutant of Cbfa1 (DeltaCbfa1). Comparison of gene expression patterns by differential display on selected SaOs-2 clones allowed the identification of four new genes that may be under the control of Cbfa1. Three of them, SelM, elF-4AI, and RPS24, seemed to be linked to a global change in cellular metabolism and cell growth. The fourth, the CD99/MIC2 gene, was strongly overexpressed (around tenfold) in cells presenting high levels of Deltacbfa1. This observation adds evidence to show that this marker of Ewing family tumors is linked to the osteoblast lineage. The exact function of CD99 remains largely undefined, and this is the first time that its regulation by an essential transcription factor involved in osteoblast differentiation has been observed.
Bertaux
Karine
K
LR2B-Laboratoire de Recherche sur les Biomatériaux et les Biotechnologies, Université du Littoral Côte d'Opale, Quai Masset, Bassin Napoléon, 62327 BP 120, Boulogne-sur-mer Cedex, France.
Broux
Odile
O
Chauveau
Christophe
C
Jeanfils
Joseph
J
Devedjian
Jean-Christophe
JC
D000071443:12E7 Antigen; D015703:Antigens, CD / Q000096:biosynthesis; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002999:Clone Cells / Q000378:metabolism; D050659:Core Binding Factor Alpha 1 Subunit; D039601:Eukaryotic Initiation Factor-4A / Q000096:biosynthesis; D006801:Humans; D009363:Neoplasm Proteins / Q000235:genetics*; D010010:Osteoclasts / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics* / Q000378:metabolism; D016133:Polymerase Chain Reaction; D011506:Proteins / Q000378:metabolism; D012269:Ribosomal Proteins / Q000096:biosynthesis; D051140:Selenoproteins; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*; D014162:Transfection; D015854:Up-Regulation
D000071443:12E7 Antigen; D015703:Antigens, CD; C061828:CD99 protein, human; D015815:Cell Adhesion Molecules; D050659:Core Binding Factor Alpha 1 Subunit; D009363:Neoplasm Proteins; D011506:Proteins; C489053:RPS24 protein, human; D012269:Ribosomal Proteins; C448999:SELM protein, human; D051140:Selenoproteins; D014157:Transcription Factors; D039601:Eukaryotic Initiation Factor-4A