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Arf Tumor Suppressor Promoter Monitors Latent Oncogenic Signals in vivo

Frederique Zindy, Richard T. Williams, Troy A. Baudino, Jerold E. Rehg, Stephen X. Skapek, John L. Cleveland, Martine F. Roussel and Charles J. Sherr
Proceedings of the National Academy of Sciences of the United States of America
Vol. 100, No. 26 (Dec. 23, 2003), pp. 15930-15935
Stable URL: http://www.jstor.org/stable/3149108
Page Count: 6
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Arf Tumor Suppressor Promoter Monitors Latent Oncogenic Signals in vivo
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Abstract

Induction of the Arf tumor suppressor gene by elevated thresholds of mitogenic signals activates a p53-dependent transcriptional response that triggers either growth arrest or apoptosis, thereby countering abnormal cell proliferation. Conversely, Arf inactivation is associated with tumor development. Expression of Arf in tissues of adult mice is difficult to detect, possibly because its induction leads to the arrest or elimination of incipient tumor cells. We replaced coding sequences of exon 1β of the mouse cellular Arf gene with a cDNA encoding GFP, thereby producing Arf-null animals in which GFP expression is driven by the intact Arf promoter. The Arf promoter was induced in several biologic settings previously shown to elicit mouse p19Arf expression. Inactivation of Arf in this manner led to the outgrowth of tumor cells expressing GFP, thereby providing direct evidence that the Arf promoter monitors latent oncogenic signals in vivo.

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