Cancer Cell
Volume 7, Issue 5, May 2005, Pages 433-444
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Article
Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation

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Summary

Checkpoints that control Myc-mediated proliferation and apoptosis are bypassed during tumorigenesis. Genes encoding polyamine biosynthetic enzymes are overexpressed in B cells from Eμ-Myc transgenic mice. Here, we report that disabling one of these Myc targets, Ornithine decarboxylase (Odc), abolishes Myc-induced suppression of the Cdk inhibitors p21Cip1 and p27Kip1, thereby impairing Myc’s proliferative, but not apoptotic, response. Moreover, lymphoma development was markedly delayed in Eμ-Myc;Odc+/− transgenic mice and in Eμ-Myc mice treated with the Odc inhibitor difluoromethylornithine (DFMO). Strikingly, tumors ultimately arising in Eμ-Myc;Odc+/− transgenics lacked deletions of Arf, suggesting that targeting Odc forces other routes of transformation. Therefore, Odc is a critical Myc transcription target that regulates checkpoints that guard against tumorigenesis and is an effective target for cancer chemoprevention.

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