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- W2117736191 abstract "Mdm2 harnesses the p53 tumor suppressor, yet loss of one Mdm2 allele in Mdm2(+/-) mice has heretofore not been shown to impair tumor development. Here we report that Mdm2 haplo-insufficiency profoundly suppresses lymphomagenesis in E micro -myc transgenic mice. Mdm2(+/-)E micro -myc transgenics had greatly protracted rates of B cell lymphoma development with life spans twice that of wild-type transgenic littermates. Im paired lymphoma development was associated with drastic reductions in peripheral B cell numbers in Mdm2(+/-)E micro -myc transgenics, and primary pre-B cells from Mdm2(+/-)E micro -myc transgenics and Mdm2(+/-) littermates were extremely susceptible to spontaneous apoptosis. Loss of p53 rescued all of the effects of Mdm2 haplo-insufficiency, indicating they were p53 dependent. Furthermore, half of the lymphomas that ultimately emerged in Mdm2(+/-)E micro -myc transgenics harbored inactivating mutations in p53, and the majority overcame haplo-insufficiency by overexpressing Mdm2. These results support the concept that Mdm2 functions are rate limiting in lymphomagenesis and that targeting Mdm2 will enhance p53-mediated apoptosis, compromising tumor development and/or maintenance." @default.
- W2117736191 created "2016-06-24" @default.
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- W2117736191 creator A5046438171 @default.
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- W2117736191 date "2003-03-17" @default.
- W2117736191 modified "2023-09-24" @default.
- W2117736191 title "Mdm2 haplo-insufficiency profoundly inhibits Myc-induced lymphomagenesis" @default.
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- W2117736191 doi "https://doi.org/10.1093/emboj/cdg133" @default.
- W2117736191 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/151074" @default.
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