CAD, a c-Myc target gene, is not deregulated in Burkitt's lymphoma cell lines

Although the Myc family of transcription factors is upregulated in many hum an tumors, it is unclear which genes are targets for the deregulated Myc. P revious studies suggest that hamster and rat carbamoyl phosphate synthase, aspartate transcarbamylase, dihydroorotase Cad genes are regulated by c-Myc . In fact, of all putative target genes thought to be activated by c-Myc, o nly the Cad gene showed loss of growth regulation in rat cells nullizygous for c-Myc. However, it was unknown whether upregulation of CAD, which perfo rms the first three rate-limiting steps of pyrimidine biosynthesis, contrib utes to c-Myc's role in human neoplasia. To explore this possibility, we cl oned the human cad promoter. We found that c-Myc could bind to an E box in the human cad promoter in gel shift assays and that growth regulated transc ription from the human cad promoter was dependent on this c-Myc binding sit e. However, the increased amount of c-Myc found in Burkitt's lymphoma cell lines did not lead to increased cad mRNA levels. Thus, we suggest that alth ough c-Myc is clearly important for the normal transcriptional control of t he cad promoter, it is unlikely that increased levels of CAD are important mediators of c-Myc-induced neoplasia. Therefore, an understanding of the me chanism by which overexpressed c-Myc contributes to the development, of Bur kitt's lymphoma requires the identification of additional c-Myc target gene s. (C) 2000 Wiley-Liss. Inc.