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

• Published in: Cancer research (Chicago, Ill.) Vol. 62; no. 1; pp. 277 - 282
• Main Authors: MIZUSHIMA, Takaaki, NAKAGAWA, Hiroshi, KAMBEROV, Yana G, WILDER, Elizabeth L, KLEIN, Peter S, RUSTGI, Anil K
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 2002
• Subjects: Animals; beta Catenin; Biological and medical sciences; Calcium-Calmodulin-Dependent Protein Kinases - antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases - metabolism; Cell physiology; Cell transformation and carcinogenesis. Action of oncogenes and antioncogenes; Cytoplasm - metabolism; Cytoskeletal Proteins - biosynthesis; Cytoskeletal Proteins - genetics; Cytoskeletal Proteins - physiology; Epidermal Growth Factor - physiology; ErbB Receptors - physiology; Esophageal Neoplasms - genetics; Esophageal Neoplasms - metabolism; Esophageal Neoplasms - pathology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation, Neoplastic; Glycogen Synthase Kinase 3; Glycogen Synthase Kinases; Humans; Molecular and cellular biology; Proto-Oncogene Proteins - physiology; Signal Transduction; TCF Transcription Factors; Trans-Activators; Transcription Factor 7-Like 2 Protein; Transcription Factors - physiology; Transcriptional Activation - physiology; Transfection; Tumor Cells, Cultured; Wnt Proteins; Wnt1 Protein; Xenopus laevis; Xenopus Proteins; Zebrafish Proteins; Human; Cell proliferation; Squamous cell carcinoma; Esophageal disease; Malignant tumor; Gene expression; In vitro; Esophagus; Signal transduction; Epidermal growth factor; Established cell line; Tumor progression; Digestive diseases; Transcription factor; Mechanism of action; Catenin; Tumor cell
• ISSN: 0008-5472; 1538-7445

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