1. Oncogenic cooperation between H-Twist and N-Myc overrides failsafe programs in cancer cells
- Author
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Philippe Leissner, Sébastien Dupasquier, Alexander Krause, Elisabeth Garin, Sandrine Valsesia-Wittmann, Anne-Catherine Jallas, Maud Magdeleine, Valérie Combaret, and Alain Puisieux
- Subjects
Cyclin-Dependent Kinase Inhibitor p21 ,Cancer Research ,Cell ,Blotting, Western ,Apoptosis ,Cell Cycle Proteins ,Biology ,Transfection ,Proto-Oncogene Proteins c-myc ,Twist transcription factor ,Mice ,Neuroblastoma ,Cell Line, Tumor ,Proto-Oncogenes ,Tumor Suppressor Protein p14ARF ,medicine ,In Situ Nick-End Labeling ,Animals ,Humans ,RNA, Small Interfering ,Cyclin-Dependent Kinase Inhibitor p16 ,Tumor Stem Cell Assay ,Oligonucleotide Array Sequence Analysis ,Caspase 8 ,Cell growth ,Microarray analysis techniques ,Caspase 3 ,Reverse Transcriptase Polymerase Chain Reaction ,Twist-Related Protein 1 ,Gene Amplification ,Nuclear Proteins ,Cell Biology ,Fibroblasts ,medicine.disease ,Blotting, Northern ,Flow Cytometry ,Gene Expression Regulation, Neoplastic ,medicine.anatomical_structure ,Cell Transformation, Neoplastic ,Oncology ,Caspases ,Cancer cell ,Cancer research ,Tumor Suppressor Protein p53 ,N-Myc ,Transcription Factors - 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.
- Published
- 2004