Correlation of BMI1 and ZEB1 expression with epithelial-mesenchymal transition in gingiva squamous cell carcinoma

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• 作者：Kinue Kurihara^a ; ^f ; ^{kuriharak@tdc.ac.jp" class="auth_mail" title="E-mail the corresponding author} ; Tomohide Isobe^b ; Gou Yamamoto^b ; Yoichi Tanaka^c ; Akira Katakura^d ; Tetsuhiko Tachikawa^e ; Takeshi Nomura^a
• 关键词：Gingiva squamous cell carcinoma ; BMI1 ; ZEB1 ; Epithelial&ndash ; mesenchymal transition
• 刊名：Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology
• 出版年：2016
• 出版时间：September 2016
• 年：2016
• 卷：28
• 期：5
• 页码：462-469
• 全文大小：2200 K

文摘

Oral squamous cell carcinoma is characterized by diverse histopathological features, tumorigenesis, and invasion. Gingiva squamous cell carcinoma (GSCC) is characterized by easily invading the jawbone. Epithelial–mesenchymal transition (EMT) is a crucial event for invasion of cancer cells and progression of carcinogenesis, inducing stem-like properties in epithelial cells. Here, expression of BMI1, which controls stem cell self-renewal, and ZEB1, a transcription factor that regulates EMT, was evaluated for its role in EMT and invasion of GSCC.

Materials and methods

We analyzed 36 gingival specimens (24 carcinomas and 12 dysplasias) by measuring protein and mRNA expression levels of BMI1, ZEB1, vimentin, and E-cadherin, and examining associations between their expression and clinicopathological parameters.

Results

Compared with adjacent normal squamous epithelium, E-cadherin expression was decreased significantly (P < 0.05) and vimentin expression levels were increased significantly (P < 0.05) at the invasive front, which are indicative of EMT in GSCC. Vimentin expression was significantly increased in poorly differentiated carcinoma (P = 0.027), and vimentin and BMI1 expression was significantly increased in grade 4 mode of invasion (P < 0.05). Furthermore, elevated levels of BMI1 were accompanied by downregulation of E-cadherin. A significant correlation was found between E-cadherin and BMI1 expression levels (P = 0.014) and between BMI1 and ZEB1 mRNA expression (P = 0.034).

Conclusion

The present study shows that the expression levels of several biomarkers of gingiva carcinogenesis have unique characteristics that differ from those in tongue carcinogenesis. BMI1 and ZEB1 may be important factors associated with EMT in the invasion and progression of GSCC.