Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factordependent transcription in esophageal cancer cells

-Catenin plays an important role in signal transduction pathways that regulate cellular differentiation and proliferation. The increased concen-tration of this protein in the cytoplasm favors its binding to the T-cell factor (TCF) family of DNA-binding proteins, and it subsequently trans-locates to the nucleus, where it induces transcription of specific genes. We explored mechanisms that lead to activation of -catenin/TCF-dependent transcription in esophageal squamous cell carcinoma (ESCC) independent of adenomatous polyposis coli and -catenin mutation. Electrophoresis mobility shift assay demonstrated that TCF4 and -catenin form a com-plex and have DNA binding activity. However, there was no constitutive activation of -catenin/TCF-dependent transcription. Coculture experi-ments demonstrated that Wnt-1, but not Wnt-5A and Wnt-7A, activated the TCF reporter gene. Additionally, when cultured with Wnt-1-condi-tioned media, ESCC cell lines showed an accumulation of -catenin in the cytoplasm. Although both Wnt and epidermal growth factor inactivate glycogen synthase kinase 3, activation of epidermal growth factor recep-tor did not stabilize -catenin. A comparison of extracellular stimuli suggests that specific Wnt family members stabilize -catenin with result-ing activation of TCF-dependent transcription in ESCC