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, Charles J. Sherr

Research output: Contribution to journalArticle

125 Scopus citations

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 p19 Arf 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.

Original languageEnglish (US)
Pages (from-to)15930-15935
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume100
Issue number26
DOIs
StatePublished - Dec 23 2003

ASJC Scopus subject areas

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    Zindy, F., Williams, R. T., Baudino, T. A., Rehg, J. E., Skapek, S. X., Cleveland, J. L., Roussel, M. F., & Sherr, C. J. (2003). Arf tumor suppressor promoter monitors latent oncogenic signals in vivo. Proceedings of the National Academy of Sciences of the United States of America, 100(26), 15930-15935. https://doi.org/10.1073/pnas.2536808100