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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, RESULTS. Meshes: Animals, Apoptosis, Blotting, Western, Cell Cycle, Cell Line, Tumor, Cell Nucleus, Cell Proliferation, Cell Shape, Cyclin-Dependent Kinase Inhibitor p21, Down-Regulation, Gene Expression, Humans, Mice, Mice, Inbred BALB C, Mice, Nude, Proto-Oncogene Proteins c-bcl-2, Receptor, Notch1, Reverse Transcriptase Polymerase Chain Reaction, S-Phase Kinase-Associated Proteins, Signal Transduction, Tongue Neoplasms, Transfection, Tumor Suppressor Protein p53, beta Catenin.
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Does growth suppression induced by Notch1 activation involve Wnt-beta-catenin down-regulation in human tongue carcinoma cells? Context: Involvement of Notch1 signalling in several cancers is well known, but its role in human tongue squamous cell carcinoma, one of the most common carcinomas of the human oral cavity, remains poorly characterized. Our studies demonstrated that constitutively over-expressed active Notch1, via stable transfection of exogenous ICN (intracellular fragment of Notch), resulted in growth suppression of the human tongue cancer cell line Tca8113 in vitro and in vivo, accompanied by G(0)-G(1) cell cycle arrest and apoptosis. Moreover, down-regulation of beta-catenin protein expression was observed in Tca8113 cells stably expressing active Notch1. Activated Notch1 also led to dramatic increase in p21(WAF1/CIP1) and p53 expression with decreases in Skp2 (S-phase kinase-associated protein 2) and Bcl-2 (B-cell lymphocytic-leukaemia proto-oncogene 2) expression, which may participate in the induction of apoptosis and cell cycle arrest.
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Since the effects of the Notch1 pathway are cell-type specific and context-dependent in cell types where Notch1 has an anti-proliferative effect, down-regulation of Wnt/beta-catenin signalling may be one of the mechanisms which induces apoptosis and cell cycle arrest. Final Decision: yes