NDLI: Dysregulation of the mTOR pathway in p53-deficient mice

Content Provider	PubMed Central
Author	Novototskaya, Liliya R. Paszkiewicz, Geraldine M. Komarova, Elena A. Leontieva, Olga V. Gudkov, Andrei V. Blagosklonny, Mikhail V.
Copyright Year	2013
Abstract	Mammalian or mechanistic target of rapamycin (mTOR) is involved in growth, aging, and age-related diseases including cancer. There is an extensive cross talk between p53 and mTOR. In cell culture, p53 inhibits the mTOR pathway in a cell type-dependent manner. p53-deficient mice develop pro-inflammation and cancer. We have shown that rapamycin delayed cancer and extended lifespan, thus partially substituting for p53. Here we show that a marker of mTOR activity, phosphorylated S6 (p-S6), is increased in the hearts of p53-deficient mice. Furthermore, cardiac p-S6 correlated with body weight. Also, p53−/− mice were slightly hyperinsulinemic with a tendency to elevated IGF-1. Radiation exacerbated the difference between IGF-1 levels in normal and p53−/− mice. Noteworthy, radiation induced Thr-308 Akt phosphorylation in the livers (but not in the hearts) of both p53+/+ and p53−/− mice. Simultaneously, radiation decreased p-S6 in the livers of normal mice, consistent with the negative effect of p53 on mTOR. Our data indicate that the activity of mTOR is increased in some but not all tissues of p53−/− mice, associated with the tendency to increased insulin and IGF-1 levels. Therefore, the absence of p53 may create oncophilic microenvironment, favoring cancer.
Related Links	http://dx.doi.org/10.4161/cbt.26947
Ending Page	1188
Page Count	7
Starting Page	1182
File Format	PDF
ISSN	15384047
e-ISSN	15558576
Journal	Cancer Biology & Therapy
Issue Number	12
Volume Number	14
Language	English
Publisher	Landes Bioscience
Publisher Date	2013-12-01
Access Restriction	Open
Rights Holder	Landes Bioscience
Subject Keyword	Molecular Medicine Cancer Research Oncology Pharmacology Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Cancer Research Pharmacology Molecular Medicine Oncology

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