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

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• 作者：Shiuan-Shinn Lee^a ; ^&dagger ; ; Chung-Hung Tsai^b ; ^c ; ^&dagger ; ; Lo-Lin Tsai^d ; Ming-Chih Chou^b ; Ming-Yung Chou^e ; Yu-Chao Chang^d ; ^e ; ^{cyc@csmu.edu.tw}
• 关键词：areca quid ; arecoline ; 尾-catenin ; oral squamous cell carcinoma ; regulatory mechanisms
• 刊名：Journal of the Formosan Medical Association
• 出版年：2012
• 期刊代码：211_09296646
• 类别：med
• 出版时间：April, 2012
• 卷：111
• 期：4
• 页码：194-200
• 文件大小：741 K

摘要

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Background/Purpose

Nuclear localization of 尾-catenin is known to associate with malignant transformation of many squamous cell carcinomas. The aim of this study was to compare 尾-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 尾-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

尾-catenin expression was significantly higher in OSCC specimens than that in normal oral epithelial specimens (p聽<聽0.05). It was demonstrated that normal oral epithelium showed only membranous staining for 尾-catenin, and membranous staining was lost or reduced with an increase in cytoplasmic/nuclear staining in OSCCs. Arecoline was found to elevate 尾-catenin expression in a dose-dependent manner (p聽<聽0.05). The addition of PD98059, NAC, herbimycin-A, SB203580, and LY294002 markedly inhibited the arecoline-induced 尾-catenin expression (p聽<聽0.05).

Conclusion

尾-catenin expression is significantly upregulated in areca quid chewing-associated OSCC. The localization of 尾-catenin expression is correlated with the tumor size and clinical stage. In addition, 尾-catenin expression induced by arecoline is downregulated by PD98059, NAC, herbimycin-A, SB203580, and LY294002.