Author/Authors :
Valsesia-Wittmann، نويسنده , , Sandrine and Magdeleine، نويسنده , , Maud and Dupasquier، نويسنده , , Sébastien and Garin، نويسنده , , Elisabeth and Jallas، نويسنده , , Anne-Catherine and Combaret، نويسنده , , Valérie and Krause، نويسنده , , Alexander and Leissner، نويسنده , , Philippe and Puisieux، نويسنده , , Alain، نويسنده ,
Abstract :
N-Myc oncogene amplification is a frequent event in neuroblastoma and is strongly correlated with advanced disease stage and treatment failure. Similarly to c-Myc oncogenic activation, N-Myc deregulation promotes both cell proliferation and p53-dependent apoptosis by sensitizing cells to a variety of insults. Intriguingly, p53 mutations are uncommon in neuroblastomas, strongly suggesting that an alternative cooperating event circumvents this safeguard against oncogene-driven neoplasia. By performing a pangenomic cDNA microarray analysis, we demonstrate that human Twist is constantly overexpressed in N-Myc-amplified neuroblastomas. H-Twist overexpression is responsible for the inhibition of the ARF/p53 pathway involved in the Myc-dependent apoptotic response. This oncogenic cooperation of two key regulators of embryogenesis causes cell transformation and malignant outgrowth.
