title: Cyclin D1-induced proliferation is independent of beta-catenin in head and neck cancer.
abstract: OBJECTIVE
  Head and neck squamous cell carcinoma (HNSCC) progression and metastasis have previously been associated with the activation of phosphatidylinositol 3-kinase-protein kinase B (PI3K-Akt) and Wnt signalling pathways, which lead to the activation of pro-proliferative genes, such as cyclin D1. The current study aims to investigate whether there is a crosstalk between these pathways in HNSCC and which pathway is more likely to regulate cyclin D1.
  
  
  METHODS
  Two HNSCC and a control keratinocyte cell lines were treated with EGF and wortmannin to respectively activate and block the PI3K-Akt and Wnt pathways. Partial and total levels of cyclin D1, beta-catenin and Akt were evaluated by Western blotting and immunofluorescence. Twenty-four paraffin-embedded samples of human HNSCC, as well as normal oral mucosa biopsies, were also immunohistochemically evaluated for beta-catenin and cyclin D1 expression.
  
  
  RESULTS
  Following both treatments, change in cyclin D1 protein was correlated with Akt levels only. Cytoplasmic staining for beta-catenin and loss of its membranous expression in the HNSCC invasive areas were found in 92% of the HNSCC biopsies.
  
  
  CONCLUSIONS
  Taken together, we show that the change in cyclin D1 levels is more likely to be due to the EGFR-Akt pathway activation than due to beta-catenin nuclear translocation.
authors.affiliation: Department of Oral Pathology, University of São Paulo School of Dentistry, São Paulo, Brazil.
authors.forename: K U
authors.initials: KU
authors.lastname: Sales
authors.forename: F S
authors.initials: FS
authors.lastname: Giudice
authors.forename: R M
authors.initials: RM
authors.lastname: Castilho
authors.forename: F T
authors.initials: FT
authors.lastname: Salles
authors.forename: C H
authors.initials: CH
authors.lastname: Squarize
authors.forename: A C
authors.initials: AC
authors.lastname: Abrahao
authors.forename: D S
authors.initials: DS
authors.lastname: Pinto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D019938:Cyclin D1 / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000473:pathology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D014407:Tumor Cells, Cultured; D051176:beta Catenin / Q000502:physiology*
chemical_list: D051176:beta Catenin; D019938:Cyclin D1; D019869:Phosphatidylinositol 3-Kinases
keywords: Akt; beta-catenin; cyclin D1; head and neck squamous cell carcinoma