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• W2034356089 abstract "Evidence that protein phosphatase 2A (PP2A) is a tumor suppressor in humans came from the discovery of mutations in the genes encoding the Aα and Aβ subunits of the PP2A trimeric holoenzymes, Aα-B-C and Aβ-B-C. One point mutation, Aα-E64D, was found in a human lung carcinoma. It renders Aα specifically defective in binding regulatory B' subunits. Recently, we reported a knock-in mouse expressing Aα-E64D and an Aα knockout mouse. The mutant mice showed a 50-60% increase in the incidence of lung cancer induced by benzopyrene. Importantly, PP2A's tumor suppressor activity depended on p53. These data provide the first direct evidence that PP2A is a tumor suppressor in mice. In addition, they suggest that PP2A is a tumor suppressor in humans. Here, we report that PP2A functions as a tumor suppressor in mice that develop lung cancer triggered by oncogenic K-ras. We discuss whether PP2A may function as a tumor suppressor in diverse tissues, with emphasis on endometrial and ovarian carcinomas, in which Aα mutations were detected at a high frequency. We propose suitable mouse models for examining whether PP2A functions as tumor suppressor in major growth-stimulatory signaling pathways, and we discuss the prospect of using the PP2A activator FTY720 as a drug against malignancies that are driven by these pathways." @default.
• W2034356089 created "2016-06-24" @default.
• W2034356089 creator A5005736421 @default.
• W2034356089 creator A5024703821 @default.
• W2034356089 date "2012-02-01" @default.
• W2034356089 modified "2023-10-18" @default.
• W2034356089 title "Mouse model for probing tumor suppressor activity of protein phosphatase 2A in diverse signaling pathways" @default.
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• W2034356089 doi "https://doi.org/10.4161/cc.11.3.19057" @default.
• W2034356089 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3315090" @default.
• W2034356089 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/22262169" @default.
• W2034356089 hasPublicationYear "2012" @default.
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