Abstract 3387: Characterization of the role of the type 2C phosphatase Ppm1d (Wip1) in metastasis

Abstract

Abstract Ppm1d (Wip1) is a member of the magnesium-dependent serine/threonine protein phosphatase family, and is considered to be an oncogene. Previous work from our lab showed that Ppm1d null mice were remarkably more resistant to oncogene driven mammary tumorigenesis. In human tumors, PPM1D amplification and overexpression are observed in multiple tumor types. In addition PPM1D amplification has often been associated with poorer prognosis than the counterpart with normal PPM1D level. Overexpression of Ppm1d in mouse embryo fibroblasts (MEFs) and in transgenic mice showed enhanced cell transformation and accelerated cancer progress. However it remains to be determined whether Ppm1d facilitates the metastasis processes. In order to address this question our lab generated a cross strain of Wip1 null and Grm1 trangenic mice. Grm1 Tg is a well-characterized mouse model for melanoma and the mice with the Grm1 transgene develop metastasis of melanoma with high frequency. Ppm1d deficiency dramatically reduced the metastasis in Grm1 Tg mice. We observed less migration efficiency in the melanoma cells with Ppm1d gene knock-down. We are investigating the known Ppm1d downstream pathways and also other signaling events to determine the potential mechanism(s). We are also extending the study to another tumor type system to determine if the pro-metastatic effect of Ppm1d is melanoma specific or not. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3387.