β-catenin expression in areca quid chewing-associated oral squamous cell carcinomas and upregulated by arecoline in human oral epithelial cells

Shiuan Shinn Lee, Chung Hung Tsai, Lo Lin Tsai, Ming Chih Chou, Ming Yung Chou, Yu Chao Chang

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Background/Purpose: 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). Conclusion: 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.

Original languageEnglish
Pages (from-to)194-200
Number of pages7
JournalJournal of the Formosan Medical Association
Volume111
Issue number4
DOIs
Publication statusPublished - Apr 2012
Externally publishedYes

Keywords

  • β-catenin
  • Areca quid
  • Arecoline
  • Oral squamous cell carcinoma
  • Regulatory mechanisms

ASJC Scopus subject areas

  • Medicine(all)

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