Abstract 1977: The protein phosphatase 2 subunit PR48 is a novel melanoma tumor suppressor gene.

Abstract

Abstract Cutaneous melanoma cell proliferation is a strong prognostic factor for distant metastasis free survival (DMFS). In the current study we tested if aberrant expression of a regulator both DNA replication and cell cycle progression, i.e. the protein phosphatase 2A subunit PR48, could be a driver of melanoma proliferation and progression. Quantitative analysis of PR48 mRNA expression revealed a strong correlation between low levels of expression and poor DMFS in a multivariate analysis (n=49, p=0.0007). In line with this, no or low PR48 protein expression was associated with poor overall survival in three independent samples sets of melanoma (n=339, P<0.001), and reduced PR48 expression correlated with increased proliferation (P=0.0023). Functional analysis using over expression and knock down strategies in melanoma cell lines demonstrated that PR48 alters cdc6-cdt1 complex formation, regulates pRb phosphorylation status, and entry into the S-phase of the cycle progression. Ectopic PR48 expression decreased tumorigenicity of melanoma cells, and shRNA-mediated reduced PR48 expression increased tumor take and growth in nude mice. Our data demonstrate that PPP2R3B is a novel tumor suppressor gene in melanoma, whose loss of expression contributes increased proliferation and poor survival. Citation Format: Léon CL van Kempen, Jonathan Jarry, Mounib Elchebly, Margaret Redpath, Per-Henrík Edqvist, Fredrik Pontén, Richard Scolyer, Dirk Schadendorf, Celia M.T. Greenwood, Joost van den Oord, Alan Spatz. The protein phosphatase 2 subunit PR48 is a novel melanoma tumor suppressor gene. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1977. doi:10.1158/1538-7445.AM2013-1977