β-catenin和Dkk-3在SD大鼠颊黏膜癌变过程中的表达

Expression of β-catenin and Dickkopf-3 in buccal mucosa carcinogenesis in Sprague-Dawley rats

目的:探讨β-catenin和Dickkopf-3(Dkk-3)蛋白表达与口腔黏膜癌变生物学行为的关系。方法:选取42例4-硝基喹啉-1-氧化物(4-introquinoline-1-oxide,4 NQO)诱发构建SD大鼠口腔黏膜癌变模型标本的存档蜡块及16例正常口腔黏膜标本,采用免疫组化法检测β-catenin蛋白及Dkk-3蛋白在SD大鼠颊黏膜癌变各阶段组织表达情况。结果:(1)随着上皮细胞异常增生程度增加到鳞状细胞癌,β-catenin的异常阳性表达率逐渐升高,β-catenin异常阳性表达率与总体相比具统计学意义(P<0.05);β-catenin的异常阳性表达率的差异与病变严重程度呈正相关关系。(2)随着上皮细胞异常增生程度增加到鳞状细胞癌,Dkk-3的阳性表达率逐渐降低。Dkk-3的阳性表达率在各组中的表达均具统计学意义(P<0.01),Dkk-3的阳性表达率与病变严重程度成负相关关系,(3)Dkk-3与β-catenin异常阳性表达率呈负相关关系。结论:Dkk-3阳性表达水平的逐渐下调和β-catenin异常阳性表达水平的逐渐上调可能与Dkk-3作为抑癌基因抑制β-catenin的异常表达密切相关。Dkk-3可能参与抑制异常激活的Wnt/β-catenin信号通路。

Objective： To investigate the association of the protein expression of β-catenin and Dickkopf-3（Dkk-3） with the biological behavior of oral mucosa carcinogenesis. Methods： A total of 42 paraffin-embedded sam-ples from Sprague-Dawley rats with oral mucosa cancer induced by 4 NQO and 16 samples of normal oral mucosawere selected. Immunohistochemistry was used to measure the protein expression of β-catenin and Dkk-3 in eachstage of buccal mucosa carcinogenesis. Results： The positive rate of β-catenin gradually increased from epithelialcell hyperplasia to squamous cell carcinoma. There was a significant difference in the positive rate of β-catenin be-tween the two groups of samples（P〈0.05）, and the difference in the positive rate of β-catenin was positively corre-lated with the severity of lesions. The positive rate of Dkk-3 gradually decreased from epithelial cell hyperplasia tosquamous cell carcinoma. There was a significant difference in the positive rate of Dkk-3 between the two groups ofsamples（P〈0.01）, and the positive rate of Dkk-3 was negatively correlated with the severity of lesions. The positiverate of Dkk-3 was negatively correlated with that of β-catenin. Conclusion： The downregulation of Dkk-3 and up-regulation of β-catenin may be associated with the fact that Dkk-3 may inhibit the abnormal expression ofβ-catenin as a tumor suppressor gene. Dkk-3 may be involved in the inhibition of the abnormally activated Wnt/β-catenin signaling pathway.