Identification of novel Myc target genes with a potential role in lymphomagenesis.

ABSTRACT

The c-Myc transcription factor regulates a wide set of genes involved in processes such as proliferation, differentiation and apoptosis. Therefore, altered expression of Myc leads to deregulation of a large number of target genes and, as a consequence, to tumorigenesis. For understanding Myc-induced transformation, identification of these target genes is essential. In this study, we searched for Myc target genes involved in lymphomagenesis using different mouse T and B cell lymphoma cell lines transformed by a conditional Myc-allele. Target genes obtained by microarray experiments were further subjected to a kinetic analysis of mRNA expression upon Myc inactivation/reactivation, bioinformatic examination of Myc binding sites and chromatin immunoprecipitation. This approach allowed us to define targets whose activation is a direct consequence of Myc binding. Among the 38 novel Myc targets, we identified several genes implicated in the tumor development. These genes are not only relevant for mouse lymphomas because we observed their upregulation in human lymphomas as well. Our findings further the understanding of Myc-induced lymphomagenesis and help toward developing more efficient antitumor strategies.