Abstract 3180: Altered β-catenin phosphorylation pattern in human prostate cancer

Abstract

Abstract Protein kinase D1 (PKD1) phosphorylates β-catenin at Thr112 and Thr120. The phosphorylation is required for β-catenin membrane trafficking via trans Golgi network (TGN). Data presented in this study indicate that activation of PKD1 shrinks the cytoplasmic pool of β-catenin which mainly is the non-phosphorylation (S33/S37/T41/S45) isoform of β-catenin, suggesting that PKD1 interacts with Wnt/GSK3β signaling pathway. The phosphorylated Thr120 β-catenin (pT120) isoform predominately locates at membrane fraction in cultured prostate cancer cell line C4-2. A newly developed phospho-threonine antibody specifically targeting the pT120 of β-catenin shows accumulation of pT120 β-catenin in TGN in normal prostate tissues. Our study demonstrates that distribution of Thr120 phosphorylated β-catenin is distinct in normal and malignant prostate tissues. In 16/22 (72%) of normal prostate tissues, the pT120 β-catenin is enriched at TGN. In contrast, only 15/200 (7.5%; p < 0.001) of prostate cancer samples had accumulation of pT120 β-catenin in TGN. A vast majority of cancer samples (92.5%) lacking of TGN staining shows the pT120 β-catenin distributed diffusely in cytoplasm, nucleus and plasma membrane. can be more discriminatory compared to conventional β-catenin antibody staining. We propose that β-catenin T120 phosphospecific antibody can be used to study alteration in subcellular distribution of β-catenin and possibly as biomarker in prostate and other tissues, which may facilitate risk stratification or predict disease outcomes. 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 3180.