The ARF tumor suppressor can promote the progression of some tumors.

Humbey O, Pimkina J, Zilfou JT, Jarnik M, Dominguez-Brauer C, Burgess DJ, Eischen CM, Murphy ME
Cancer Res. 2008 68 (23): 9608-13

PMID: 19047137 · PMCID: PMC2637809 · DOI:10.1158/0008-5472.CAN-08-2263

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.

MeSH Terms (15)

Animals Autophagy Cyclin-Dependent Kinase Inhibitor p16 Disease Progression Fibroblasts Genes, Tumor Suppressor Gene Silencing Humans Lymphoma, B-Cell Mice Mice, Knockout Mice, SCID RNA, Messenger Tumor Suppressor Protein p53 Up-Regulation

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