title: β-catenin expression in areca quid chewing-associated oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells.
abstract: OBJECTIVE
  Nuclear localization of β-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare β-catenin expression in normal human oral epithelium and areca quid chewing associated oral squamous cell carcinomas (OSCCs) and further to explore the potential mechanisms that may lead to induce β-catenin expression.
  
  
  METHODS
  A total of 40 areca quid chewing-associated OSCCs and 10 normal oral tissue biopsy samples without areca quid chewing were analyzed by immunohistochemistry. The oral epithelial cell line GNM cells were challenged with arecoline, a major areca nut alkaloid, by using Western blot analysis. Furthermore, extracellular signal-regulated protein kinase inhibitor PD98059, glutathione precursor N-acetyl-l-cysteine (NAC), tyrosine kinase inhibitor herbimycin-A, p38 inhibitor SB203580, and phosphatidylinositaol 3-kinase inhibitor LY294002 were added to find the possible regulatory mechanisms.
  
  
  RESULTS
  β-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p < 0.05). It was demonstrated that normal oral epithelium showed only membranous staining for β-catenin, and membranous staining was lost or reduced with an increase in cytoplasmic/nuclear staining in OSCCs. Arecoline was found to elevate β-catenin expression in a dose-dependent manner (p < 0.05). The addition of PD98059, NAC, herbimycin-A, SB203580, and LY294002 markedly inhibited the arecoline-induced β-catenin expression (p < 0.05).
  
  
  CONCLUSIONS
  β-catenin expression is significantly upregulated in areca quid chewing-associated OSCC. The localization of β-catenin expression is correlated with the tumor size and clinical stage. In addition, β-catenin expression induced by arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002.
authors.affiliation: School of Public Health, Chung Shan Medical University, Taichung, Taiwan.
authors.forename: Shiuan-Shinn
authors.initials: SS
authors.lastname: Lee
authors.forename: Chung-Hung
authors.initials: CH
authors.lastname: Tsai
authors.forename: Lo-Lin
authors.initials: LL
authors.lastname: Tsai
authors.forename: Ming-Chih
authors.initials: MC
authors.lastname: Chou
authors.forename: Ming-Yung
authors.initials: MY
authors.lastname: Chou
authors.forename: Yu-Chao
authors.initials: YC
authors.lastname: Chang
mesh_terms: D000328:Adult; D000368:Aged; D001114:Areca / Q000009:adverse effects*; D001115:Arecoline / Q000009:adverse effects* / Q000378:metabolism; D001706:Biopsy; D015153:Blotting, Western; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008409:Mastication; D008875:Middle Aged; D009061:Mouth Mucosa / Q000378:metabolism* / Q000473:pathology; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation; D051176:beta Catenin / Q000378:metabolism*
chemical_list: D051176:beta Catenin; D001115:Arecoline; D048049:Extracellular Signal-Regulated MAP Kinases