Title of article
Inhibition of RNA Polymerase I as a Therapeutic Strategy to Promote Cancer-Specific Activation of p53
Author/Authors
Bywater، نويسنده , , Megan J. and Poortinga، نويسنده , , Gretchen and Sanij، نويسنده , , Elaine and Hein، نويسنده , , Nadine and Peck، نويسنده , , Abigail and Cullinane، نويسنده , , Carleen and Wall، نويسنده , , Meaghan and Cluse، نويسنده , , Leonie and Drygin، نويسنده , , Denis and Anderes، نويسنده , , Kenna and Huser، نويسنده , , Nanni and Proffitt، نويسنده , , Chris and Bliesath، نويسنده , , Joshua and Haddach، نويسنده , , Mustapha and Schwaebe، نويسنده , , Michael K. and Ryckman، نويسنده , , David M. and Rice، نويسنده , , William G. and Schmitt، نويسنده , , Clemens and Lowe، نويسنده , , Scott W. and Johnstone، نويسنده , , Ricky W. and Pearson، نويسنده , , Richard B. and McArthur، نويسنده , , Grant A. and Hannan، نويسنده , , Ross D.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2012
Pages
15
From page
51
To page
65
Abstract
Summary
sed transcription of ribosomal RNA genes (rDNA) by RNA Polymerase I is a common feature of human cancer, but whether it is required for the malignant phenotype remains unclear. We show that rDNA transcription can be therapeutically targeted with the small molecule CX-5461 to selectively kill B-lymphoma cells in vivo while maintaining a viable wild-type B cell population. The therapeutic effect is a consequence of nucleolar disruption and activation of p53-dependent apoptotic signaling. Human leukemia and lymphoma cell lines also show high sensitivity to inhibition of rDNA transcription that is dependent on p53 mutational status. These results identify selective inhibition of rDNA transcription as a therapeutic strategy for the cancer specific activation of p53 and treatment of hematologic malignancies.
Journal title
Cancer Cell
Serial Year
2012
Journal title
Cancer Cell
Record number
1337954
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