| First Author | Walter G | Year | 2012 |
| Journal | Cell Cycle | Volume | 11 |
| Issue | 3 | Pages | 451-9 |
| PubMed ID | 22262169 | Mgi Jnum | J:182425 |
| Mgi Id | MGI:5315400 | Doi | 10.4161/cc.11.3.19057 |
| Citation | Walter G, et al. (2012) Mouse model for probing tumor suppressor activity of protein phosphatase 2A in diverse signaling pathways. Cell Cycle 11(3):451-9 |
| abstractText | Evidence that protein phosphatase 2A (PP2A) is a tumor suppressor in humans came from the discovery of mutations in the genes encoding the Aalpha and Abeta subunits of the PP2A trimeric holoenzymes, Aalpha-B-C and Abeta-B-C. One point mutation, Aalpha-E64D, was found in a human lung carcinoma. It renders Aalpha specifically defective in binding regulatory B' subunits. Recently, we reported a knock-in mouse expressing Aalpha-E64D and an Aalpha 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 Aalpha 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. |
