Characterization of the Subcellular Distribution of Phospho-β-catenin in Colorectal Cancer.

Abstract

β-Catenin is a multifunctional protein, which is localized to different subcellular compartments of the normal colon epithelium. The hyperactivation of Wnt pathway results in the nuclear accumulation of β-catenin and induction of colorectal carcinogenesis. Although N-terminally hypo-phosphorylated β-catenin (active β-catenin) is known as the transcriptionally active form, phospho-S33/S37/T41-β-catenin (phospho-β-catenin) can also accumulate in the nucleus. In this study, we aimed to characterize the subcellular distribution of phospho-β-catenin and the other forms of β-catenin in normal colon epithelium and colorectal cancer (CRC). Phosphorylated, hypo-phosphorylated, and the total pool of β-catenin were evaluated in colon epithelium and CRC using immunohistochemistry, immunofluorescence staining, and western blotting. Tissue microarrays were used to determine the expression pattern of phospho-β-catenin in CRC samples. Almost 11% (49/452) of CRCs expressed moderate to high levels of phospho-β-catenin in the nucleus. In addition, hypo-phosphorylated and phosphorylated forms of β-catenin localized to different subcellular regions in normal colon epithelium and CRC. Immunoblotting experiments suggested that truncated phospho-β-catenin forms can be found in CRCs. Phospho-β-catenin accumulates in the nucleus and different molecular weight β-catenin proteins are present in colon cancer cells. To elaborate on the functional significance of nuclear phospho-β-catenin, further studies should be performed.