Down-regulation of β-catenin TCF signaling is linked to colonic epithelial cell differentiation

Abstract

The β-catenin TCF pathway is implicated in the regulation of colonic epithelial cell proliferation, but its role in the regulation of cell differentiation is unknown. The colon carcinoma cell line, Caco-2, spontaneously undergoes Go/G1 cell cycle arrest and differentiates along the absorptive cell lineage over 21 days in culture. In parallel, we show that β-catenin-TCF activity and complex formation are significantly down-regulated. The down-regulation of β-catenin-TCF signaling was independent of APC, which we characterized as having a nonsense mutation in codon 1367 in Caco-2 cells, but was associated with a decrease in TCF-4 protein levels. Total β-catenin levels increased during Caco-2 c..