title: Growth suppression induced by Notch1 activation involves Wnt-beta-catenin down-regulation in human tongue carcinoma cells.
abstract: BACKGROUND
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan, Hubei 430079, People's Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Duan
authors.forename: Jun
authors.initials: J
authors.lastname: Yao
authors.forename: Xinxing
authors.initials: X
authors.lastname: Wu
authors.forename: Mingwen
authors.initials: M
authors.lastname: Fan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000737:chemistry / Q000378:metabolism; D049109:Cell Proliferation; D048430:Cell Shape / Q000235:genetics / Q000502:physiology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D015536:Down-Regulation; D015870:Gene Expression / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051881:Receptor, Notch1 / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D044786:S-Phase Kinase-Associated Proteins / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology*; D014062:Tongue Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014162:Transfection; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C000715470:MAS1 protein, human; C497761:NOTCH1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D051881:Receptor, Notch1; D044786:S-Phase Kinase-Associated Proteins; D016159:Tumor Suppressor Protein p53; D051176:beta Catenin