C-MYC INDUCES THE EXPRESSION AND ACTIVITY ORNITHINE DECARBOXYLASE

The role of the product of the c-myc protooncogene in the regulation of cellular proliferation and differentiation is well established. Recent reports that c-Myc can serve as a sequence-specific transcriptional activator have begun to elucidate the mechanism by which c-Myc exerts such a profound effect on the mitotic status of a cell. To identify a potential target gene for Myc-mediated trans-activation, we examined the regulation of the ornithine decarboxylase (ODC) gene by c-Myc. ODC is the first and rate-limiting enzyme involved in the synthesis of the polyamines and has been shown to be required for entry into and progression through the cell cycle. Using a conditionally active c-Myc-estrogen receptor chimeric protein, we found estrogen-dependent activation of ODC expression and enzymatic activity. The induction of ODC mRNA expression was not dependent upon de novo protein synthesis. These data suggest that one downstream pathway for Myc-directed cell cycle control is the induction of ODC expression.