p120-连接素介导钙抑制鳞状上皮细胞癌变的作用

发布时间：2018-04-26 15:26

本文选题：钙 + p120-连接素　；参考：《中南大学》2014年硕士论文

【摘要】：目的：钙是机体内含量最丰富的矿物质,能构成骨骼和牙齿,维持神经肌肉兴奋性,调节肌肉收缩和舒张、凝血及腺体分泌。近年来发现钙还能调节上皮细胞的增殖与分化,提示钙可能有抑制上皮肿瘤的非经典作用。有研究发现,钙能够诱导细胞膜上的E一钙粘素/p120-连接素/p-连接素复合物的形成并激活一系列信号通道引起细胞内钙增加诱导细胞分化。钙粘素/连接素复合物的稳定性依赖于p120-连接素的存在。本研究通过观察致癌物诱导的不同钙饮食口腔粘膜特异性p120-连接素敲除小鼠的口腔鳞状上皮细胞增殖和分化水平,来确定p120-连接素是否介导钙抑制增生和促进分化的作用,探讨饮食钙抑制鳞状上皮细胞癌变机制,为防治鳞癌药物的开发提供重要的理论依据。方法：为明确p120-连接素是否介导钙调节口腔鳞状上皮细胞增殖及分化的作用,本研究通过免疫组化实验方法观察小鼠口腔粘膜p120-连接素敲除后,不同钙饮食对致癌物4NQO诱导的小鼠口腔鳞状上皮细胞增殖和分化水平的影响,另外我们还观察了p120-连接素敲除后不同钙饮食对小鼠口腔鳞状上皮细胞E-钙粘素、β-连接素和PLC-γ1表达水平的影响。结果：(1)经用免疫组织化学染色方法,我们证实了p120-连接素敲除的小鼠口腔粘膜内的p120-连接素染色呈现阴性。(2)小鼠口腔粘膜p120-连接素敲除后,饮食钙抑制增生与促进分化作用减弱,表明p120-连接素介导了饮食钙促进口腔鳞状上皮细胞分化及抑制口腔鳞状上皮细胞增生的作用。(3)饮食钙能够增加小鼠正常口腔鳞状上皮的E-钙粘素和β-连接素表达水平,并且能够降低PLC-γ1表达水平,而小鼠口腔粘膜p120-连接素敲除后饮食钙这一作用减弱,表明p120-连接素介导饮食钙促进E-钙粘素和β-连接素的表达水平及饮食钙降低了PLC-γ1表达水平的作用。结论：我们的研究结果表明p120-连接素介导饮食钙调节口腔鳞状上皮细胞增殖和分化的作用,这一作用可能参与钙抑制鳞状上皮细胞癌变的过程。
[Abstract]:Objective: calcium is the most abundant mineral in the body, which can form bone and teeth, maintain neuromuscular excitability, regulate muscle contraction and relaxation, blood clotting and glandular secretion. In recent years, it has been found that calcium can also regulate the proliferation and differentiation of epithelial cells, suggesting that calcium may have a nonclassical effect on inhibiting epithelial tumors. It has been found that calcium can induce the formation of E-cadherin / p120-catenin complex and activate a series of signal channels to induce cell differentiation. The stability of the cadherin / catenin complex depends on the existence of p120-catenin. In this study, we observed the proliferation and differentiation level of oral squamous epithelium cells induced by carcinogens in different calcium diet specific p120-catenin knockout mice to determine whether p120-catenin mediates the role of calcium in inhibiting proliferation and promoting differentiation. To explore the mechanism of dietary calcium inhibiting squamous cell carcinogenesis and provide important theoretical basis for the development of drugs for the prevention and treatment of squamous cell carcinoma. Methods: in order to determine whether p120-catenin mediates the role of calcium in regulating the proliferation and differentiation of oral squamous epithelium cells, the present study was conducted to observe the effect of p120-catenin knockout on mouse oral mucosa by immunohistochemical method. Effects of different calcium diets on proliferation and differentiation of oral squamous epithelial cells induced by carcinogen 4NQO in mice. In addition, we also observed the effects of different calcium diets on the expression of E-cadherin, 尾 -catenin and PLC- 纬 _ 1 in mouse oral squamous epithelial cells after p120-catenin knockout. Results by immunohistochemical staining, we confirmed that p120-catenin staining was negative in the oral mucosa of mice with p120-catenin knockout. Dietary calcium inhibits proliferation and promotes differentiation. It is suggested that dietary calcium can promote the differentiation of oral squamous epithelial cells and inhibit the proliferation of oral squamous epithelial cells. Dietary calcium can increase the expression of E-cadherin and 尾 -catenin in normal oral squamous epithelium of mice. The expression level of PLC- 纬 1 was decreased, but the effect of dietary calcium was decreased after p120-catenin knockout in mouse oral mucosa. The results indicated that dietary calcium mediated by p120-catenin promoted the expression of Ecadherin and 尾 -catenin and decreased the expression of PLC- 纬 1 in diet. Conclusion: our results suggest that dietary calcium mediates the proliferation and differentiation of oral squamous epithelial cells mediated by p120-catenin, which may be involved in the inhibition of squamous cell carcinogenesis by calcium.
【学位授予单位】：中南大学
【学位级别】：硕士
【学位授予年份】：2014
【分类号】：R739.8

【共引文献】