The ARF Tumor Suppressor Can Promote the Progression of Some Tumors

Humbey, O., Pimkina, J., Zilfou, J. T., Jarnik, M., Dominguez-Brauer, C., Burgess, D. J., Eischen, C. M., Murphy, M. E. (December 2008) The ARF Tumor Suppressor Can Promote the Progression of Some Tumors. Cancer Res, 68 (23). pp. 9608-9613.

URL: http://www.ncbi.nlm.nih.gov/pubmed/19047137
DOI: 10.1158/0008-5472.can-08-2263

Abstract

p14/p19ARF (ARF) is a tumor suppressor gene that is frequently mutated in human cancer. ARF has multiple tumor suppressor functions, some of which are mediated by signaling to p53. Surprisingly, a significant fraction of human tumors retain persistently high levels of ARF, suggesting that ARF may possess a prosurvival function. We show that ARF protein is markedly up-regulated in cells exposed to nutrient starvation. Cells with silenced ARF show reduced autophagy and reduced viability when placed under conditions of starvation. We show for the first time that ARF silencing can limit the progression of some tumors, such as lymphoma, but not others, such as E1A/Ras-induced tumors. Specifically, myc-driven lymphomas with mutant p53 tend to overexpress ARF; we show that silencing ARF in these tumors greatly impedes their progression. These data are the first to show that ARF can act in a p53-independent manner to promote the progression of some tumors. [Cancer Res 2008;68(23):9608-13]

Item Type: Paper
Uncontrolled Keywords: ARF mitochondria autophagy
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types > ARF
diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
diseases & disorders
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function > genes: types
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > suppressor
CSHL Authors:
Communities: CSHL labs > Lowe lab
Watson School > Publications
Depositing User: Matt Covey
Date: 1 December 2008
Date Deposited: 28 Feb 2013 15:34
Last Modified: 26 Sep 2014 18:45
PMCID: PMC2637809
Related URLs:
URI: http://repository.cshl.edu/id/eprint/27492

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