Wnt-1 but not epidermal growth factor induces beta-catenin/T-cell factor-dependent transcription in esophageal cancer cells.
Cancer Res
; 62(1): 277-82, 2002 Jan 01.
Article
em En
| MEDLINE
| ID: mdl-11782388
ABSTRACT
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.
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Base de dados:
MEDLINE
Assunto principal:
Fatores de Transcrição
/
Neoplasias Esofágicas
/
Transativadores
/
Proteínas Proto-Oncogênicas
/
Proteínas do Citoesqueleto
/
Proteínas de Peixe-Zebra
/
Fator de Crescimento Epidérmico
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Cancer Res
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos