Journal
ORAL ONCOLOGY
Volume 48, Issue 1, Pages 33-39Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.oraloncology.2011.08.008
Keywords
beta-Catenin; DMBA; Hamster buccal pouch; Wnt
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Wnt signaling pathway mediated via interactions between beta-catenin and members of the TCF/LEF-1 family of transcription factors plays a central role in the regulation of epithelial cell proliferation, apoptosis, differentiation, adhesion, epithelial-mesenchymal transition, and invasion. Aberrant activation of the Wnt/beta-catenin signaling pathway with overexpression of Wnt and Fz, mutations of APC, beta-catenin, and axin 1, and cytoplasmic accumulation of beta-catenin have been frequently reported in a broad spectrum of human malignancies including oral squamous cell carcinomas (OSCCs). However, changes in the components of the Wnt signaling pathway have not been documented during 7,12-dimethylbenz[a]anthracene (DMBA)-induced hamster buccal pouch (HBP) carcinogenesis, a paradigm for oral oncogenesis and chemointervention. In this study, we evaluated the role of beta-catenin accumulation and Wnt ligands, Wnt signaling members (Fz, Dvl, APC, GSK-3 beta, axin, and WIF) and the downstream targets of Wnt (cyclin D1, MMP-2, and MMP-9) during the sequential progression of DMBA-induced HBP carcinomas by semi-quantitative RT-PCR and western blot analyses. Our data reveal a correlation between beta-catenin accumulation and activation of Wnt signaling, and its downstream effector molecules during the sequential development of HBP carcinomas from hyperplasia to invasive carcinoma through dysplasia. Our data also support a pivotal role for beta-catenin in the malignant transition of the HBP. Aberrant Wnt signaling may be a hallmark of progression to malignancy during DMBA-induced HBP carcinogenesis and could be a potential preventive and therapeutic target for suppression of OSCC. (C) 2011 Elsevier Ltd. All rights reserved.
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