Author/Authors :
Nilsson، نويسنده , , Jonas A. and Keller، نويسنده , , Ulrich B. and Baudino، نويسنده , , Troy A. and Yang، نويسنده , , Chunying and Norton، نويسنده , , Sara and Old، نويسنده , , Jennifer A. and Nilsson، نويسنده , , Lisa M. and Neale، نويسنده , , Geoffrey and Kramer، نويسنده , , Debora L. and Porter، نويسنده , , Carl W. and Cleveland، نويسنده , , John L.، نويسنده ,
Abstract :
Summary
oints 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.
