bHLH transcription factors in differentiating neuroblastoma cells

Abstract: Neuroblastoma is a tumor of the sympathetic nervous system, and arises during early childhood. The tumor is highly heterogeneous and evidence, such as expression of genes normally only expressed during embryonic and fetal stages, suggests that the tumor is of embryonic origin and that the tumor arises as a consequence of perturbed differentiation during the development of the sympathetic nervous system. Transcription factors implicated in this differentiation program are therefore of potential interest in order to understand the genesis of neuroblastoma. Based on findings in Drosophila, several transcription factors playing vital roles in the development of the vertebrate peripheral nervous system have been identified, some of them belonging to the basic helix-loop-helix (bHLH) family. Amplification of the protooncogene N-Myc is one of the most important genetic aberrations in neuroblastoma. There is a high positive correlation between N-Myc amplification and malignancy, but the molecular consequences of this phenomenon have only been partly investigated. The work presented here describes the roles of the bHLH transcription factors HASH-1, HES-1, and the bHLHZip transcription factors N-Myc, Mad proteins, Mnt/Rox, and Max during neuroblastoma cell differentiation. It suggests that a controlled temporal expression patterns of some of these genes are important in order to allow neuronal differentiation to proceed.