Involvement of Myc targets in c-myc and N-myc induced human tumors.

The myc proto-oncogenes are transcription factors that directly regulate the expression of other genes, by binding to the specific DNA sequence, CACGTG. Among the target genes for c-Myc regulation are ECA39, p53, ornithine decarboxylase (ODC), alpha-prothymosin and Cdc25A. In this study we examined the involvement of c-Myc target genes in human oncogenesis induced by c-myc or N-myc. In MCF-7 breast cancer cells, the induction of c-myc expression by estrogen was followed by the induction of all the Myc targets that we examined, indicating that those genes can serve as c-Myc targets in human oncogenesis. Moreover, in breast tumors exhibiting c-myc overexpression, several Myc targets were also overexpressed. A clear correlation between the expression of c-myc and its targets was also detected in Burkitt's lymphomas, which involve a specific translocation of c-myc gene, but not in other lymphoma cells. Yet, in cells derived from a neuronal origin the pattern of expression of Myc targets was more complex. In a neuroepithelioma cell line that overexpresses c-myc, only some targets were expressed. In addition in neuroblastomas, in which N-myc is amplified and overexpressed, only ODC was overexpressed in all cell lines, while all other target genes were expressed in only some of the cell lines. The more complex expression pattern found for the Myc targets in neuroblastomas suggests that genes that were identified originally as targets for c-Myc regulation may be regulated by N-Myc, but other cell specific factors are also needed for transcription of the target genes.