Overproduction of ornithine decarboxylase confers an apparent growth advantage to mouse tumor cells.

We have selected mouse myeloma and leukemia cell lines overproducing ornithine decarboxylase (ODC) under the pressure of alpha-difluoromethylornithine (DFMO), a mechanism-based inhibitor of the enzyme. Two of the tumor cell variants overproduced ODC by virtue of an amplification of transcriptionally active ODC genes. In one case the overproduction of the enzyme was based on an enhanced transcription of the enzyme's message at normal gene copy number. The DFMO-resistant cells exhibited ODC activity that was 8 to 25 times higher than the enzyme activity in the parental cells. When plated into soft agar, the parental mouse myeloma cells failed to form any colonies, whereas the ODC overproducing variant cells grew soft agar at a plating efficiency of about 16%. The difference between parental and ODC overproducing cells was even more striking in case of mouse leukemia L1210 cells. The parental L1210 cell formed colonies in soft agar at an efficiency of 1.9% while two overproducer variant cell lines formed colonies at up to 60% plating efficiency. These results clearly indicate that an overproduction of ODC offers a distinct growth advantage to tumor cells.