Identification of c-Myc responsive genes using rat cDNA microarray

c-Myc functions; through direct activation or repression of transcription. Using cDNA microarray analysis, we have identified c-Mj c-responsive genes by comparing gene expression profiles between c-myc null and c-myc wildtype rat fibroblast cells and between c-myc null and c-myc nub cells reconstitu ted with c-myc. From a panel of 4400 cDNA elements, we found 198 genes resp onsive to c-myc when comparing wild-type or reconstituted cells with the nu ll cells. The plurality of the named c-Myc-responsive genes that were up-re gulated, including 30 ribosomal protein genes, are involved in macromolecul ar synthesis and metabolism, suggesting a major role of c-Myc in the regula tion of protein synthetic and metabolic pathways. When ectopically overexpr essed, c-Myc induced a different and smaller set of c-Myc-responsive genes as compared with the physiologically expressed c-Myc condition. Thus, these results from expression profiling suggest a new primary function for c-Myc and raise the possibility that the physiological and transforming function s of c-myc may be separable.