Wnt/beta-catenin/Tcf signaling pathway activation in malignant progression of rat gliomas induced by transplacental N-ethyl-N-nitrosourea exposure.

摘要

Although Wnt/beta-catenin/Tcf signaling pathway has been shown to be a crucial factor in the development of many cancers, little is known about its role in glioma malignancy. In the present study, we report the first evidence that Wnt/beta-catenin/Tcf signaling pathway is constitutively activated in experimental gliomas induced by single transplacental dose of N-ethyl-N-nitrosourea (ENU). In the present study we analyzed ENU induced rat gliomas of different stages (P90, P135 and P180) for the expression of beta-catenin, Lef1, Tcf4 and their targets c-Myc, N-Myc and cyclin D1. Western blot analysis revealed upregulation of beta-catenin, Lef1, Tcf4, c-Myc, N-Myc and cyclin D1 in gliomas compared to controls and their levels were progressively increased from initial stage (P90) to progression stage (P180). In consistent with this, immunohistochemistry revealed the cytoplasmic and nuclear accumulation of beta-catenin, and nuclear positivity was evident for Lef1, Tcf4, c-Myc, N-Myc and cyclin D1. Based on these results, we conclude that Wnt/beta-catenin pathway may play a major role in the tumorigenesis and tumor progression in ENU induced rat gliomas.