[PDF][PDF] Targeting ornithine decarboxylase in Myc-induced lymphomagenesis prevents tumor formation

JA Nilsson, UB Keller, TA Baudino, C Yang, S Norton… - Cancer cell, 2005 - cell.com
JA Nilsson, UB Keller, TA Baudino, C Yang, S Norton, JA Old, LM Nilsson, G Neale…
Cancer cell, 2005cell.com
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
p21 Cip1 and p27 Kip1, thereby impairing Myc's proliferative, but not apoptotic, response.
Moreover, lymphoma development was markedly delayed in Eμ-Myc; Odc+/− transgenic …
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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